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VASCULAR ENDOTHELIAL GROWTH FACTOR C PREPROPROTEIN
LATEST LITERATURE
1: Journal of surgical oncology, 2010 Jul 29,
Predictive significance of preoperative serum VEGF-C and VEGF-D, independently and combined with Ca19-9, for the presence of malignancy and lymph node metastasis in patients with gastric cancer.
[Abstract]BACKGROUND: Cumulative evidence demonstrate that lymphangiogenic vascular endothelial growth factors (VEGF)-C and -D are over-expressed and associated to lymph node metastasis (LNM) in gastric cancer. The aim of this study is to investigate whether preoperative serum levels of VEGF-C and VEGF-D could be useful tumor markers in patients with operable gastric adenocarcinoma. METHODS: We prospectively examined serum samples from 40 patients and 40 non-cancer controls using enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was implemented. VEGF-C and VEGF-D were studied independently and in combination with Ca19-9. RESULTS: In gastric cancer patients, preoperative VEGF-C was significantly lower as compared to controls and to postoperative VEGF-C (P < 0.001); preoperative VEGF-D was significantly higher as compared to controls and to postoperative VEGF-D (P < 0.001). ROC curve analysis identified a VEGF-C/VEGF-D cut-off value of <2.7 for the presence of gastric cancer, with 83% sensitivity and 75% specificity (P < 0.001). Backward stepwise selection modeling including sex, age, VEGF-D and Ca19-9, predicted the presence of LNM with 86% sensitivity and 82% specificity (P < 0.001). CONCLUSION: Circulating levels of VEGF-C and VEGF-D could play a role as biomarkers for serological detection and staging in gastric cancer. J. Surg. Oncol. (c) 2010 Wiley-Liss, Inc.
2: Blood, 2010 Jun 3, 25(7)
High VEGFC expression is associated with unique gene expression profiles and predicts adverse prognosis in pediatric and adult acute myeloid leukemia.
[Abstract]High VEGFC mRNA expression of AML blasts is related to increased in vitro and in vivo drug resistance. The prognostic significance of VEGFC on long-term outcome and its associated gene expression profiles remain to be defined. We studied the effect of VEGFC on treatment outcome and investigated gene expression profiles associated with VEGFC using microarray data of 525 adult and 100 pediatric AML patients. High VEGFC expression appeared strongly associated with reduced complete remission rate (P = .004), reduced overall and event-free survival (OS and EFS) in adult AML (P = .002 and P <.001 respectively). Multivariable analysis established high VEGFC as prognostic indicator independent of cytogenetic risk, FLT3-ITD, NPM1, CEBPA, age and WBC (P = .038 for OS and P = .006 for EFS). Also in pediatric AML high VEGFC was related to reduced OS (P = .041). A unique series of differentially expressed genes was identified that distinguished AML with high VEGFC from AML with low VEGFC, i.e., 331 upregulated genes (representative of proliferation, VEGF-receptor activity, signal transduction) and 44 downregulated genes (e.g. related to apoptosis) consistent with a role in enhanced chemoresistance. In conclusion, high VEGFC predicts adverse long-term prognosis and provides prognostic information in addition to well-known prognostic factors.
3: Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery, 2010 Feb, 24(3)
[Expression and relationship of EBV LMP1, COX-2 and VEGF-C in nasopharyngeal carcinoma]
[Abstract]OBJECTIVE: To evaluate the expression of vascular endothelial growth factor C (VEGF-C), Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), cyclooxygenase-2 (COX-2) in nasopharyngeal carcinoma (NPC). METHOD: LMP1, COX-2 and VEGF-C were detects by immunohistochemical staining for 57 case NPC tissue. RESULT: The positives rates of LMP1, COX-2 and VEGF-C detected by immunohistochemical staining were 49.1% (28/57), 75.4% (43/57) and 59.6% (34/57), respectively. The expression of LMP1, COX-2 and VEGF-C were correlated to each other in NPC (P < 0.05). CONCLUSION: LMP1 and COX-2 may induce expression of VEGF-C directly or LMP1 induce expression of VEGF-C by induce COX-2 expression, may contribute to lymph metasta sis and develop NPC.
4: The Biochemical journal, 2010 Apr 26, 21(2)
Characterization of novel vascular endothelial growth factor (VEGF)-C splicing isoforms from mouse.
[Abstract]Vascular endothelial growth factor (VEGF)-C is a major growth factor implicated in various physiological processes such as angiogenesis and lymphangiogenesis. Here, we report the identification of three short VEGF-C splicing isoforms (VEGFC62, VEGFC129 and VEGFC184) from immortalized mouse kidney proximal tubular epithelial cells (PTECs). Semi-quantitative RT-PCR analysis showed these isoforms were universally expressed to varying degrees in different tissues with high expression levels in the kidney. In immortalized PTECs and podocytes, VEGFC62 can activate phosphorylation of focal adhesion kinase (FAK) and promote cell adhesion to substratum. Cell survival was also increased by VEGFC62 treatment in the absence of serum. VEGFC62 can also reduce cell proliferation in PTECs and podocytes. Nucleolin was one of the proteins that associate with VEGFC62 in pull-down assay using GST fusion protein as bait, indicating different protein binding requirement for VEGFC62 than VEGF-C. In conclusion, these newly identified VEGF-C isoforms represent a new class of proteins, potentially involved in epithelial cell adhesion and proliferation through novel receptor pathways.
5: Anatomical record (Hoboken, N.J. : 2007), 2010 Mar 11,
Expression of VEGF-C and VEGF-D as Significant Markers for Assessment of Lymphangiogenesis and Lymph Node Metastasis in Non-Small Cell Lung Cancer.
[Abstract]Vascular endothelial growth factor (VEGF)-C and VEGF-D induce lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3) and have been implicated in tumor spread to the lymphatic system. Lymph node dissemination critically determines clinical outcome and therapeutic options of patients with non-small cell lung cancer (NSCLC). However, the relationship of VEGF-C, VEGF-D, and lymph node metastasis in cancers, including NSCLC, is still controversial. To evaluate the relationship between lymphangiogenesis and lymph node metastasis, the expression of VEGF-C and VEGF-D in NSCLC tumors were detected by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). QRT-PCR revealed that in marginal region VEGF-C and VEGF-D mRNA was significantly higher than in tumor center, and VEGF-D mRNA was also higher than that in peritumoral lung tissue. Immunohistochemically, we observed the same heterogeneous expression of VEGF-C and VEGF-D proteins. The group with high expression of VEGF-C and VEGF-D in marginal region had a higher incidence of lymph node metastasis compared with the group with low expression. Furthermore, the group with high expression of VEGF-D in marginal region had a higher incidence of lymphatic invasion. The group with high peritumoral lymphatic vessel density (LVD) had higher expression of VEGF-C and VEGF-D mRNA compared with the group with low peritumoral LVD. Our studies suggested that the expression of VEGF-C and VEGF-D at invasive edge was significantly associated with lymph node metastasis or lymphatic invasion in patients with NSCLC and may be involved in regulation of lymphangiogenesis and lymph node metastasis in NSCLC. Anat Rec, 2010. (c) 2010 Wiley-Liss, Inc.
6: Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery, 2009 Oct, 23(19)
[Expression of COX-2 and VEGF-C in papillary thyroid carcinoma and their relationship to cervical lymph metastases]
[Abstract]OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C) in papillary thyroid carcinoma and their relationship to cervical lymph metastases. METHOD: In this study, the expressions of COX-2 and VEGF-C were examined by immunohistochemistry in papillary thyroid carcinoma tissues of 40 patients, and analysis was performed on the correlation of cervical lymph metastases with COX-2 and VEGF-C expression. RESULT: Positive expressions of COX-2 and VEGF-C were 70.0% (28/40) and 75.0% (30/40) respectively in papillary thyroid carcinoma. The positive rates of COX-2 and VEGF-C expression were 80.8% (21/26) and 84.6% (22/26) respectively in patients with cervical lymph metastases, and 50.0% (7/14) and 57.1% (8/14) respectively in patients without cervical lymph metastases, with a statistically significant difference between two groups (P<0.05, all). COX-2 was positively correlated to VEGF-C expression in papillary thyroid carcinoma (r=0.378, P<0.05). CONCLUSION: The results suggest that COX-2 and VEGF-C were highly expressed in papillary thyroid carcinoma, with possible interaction of their expressions, and may play a critical role in the cervical lymph metastases of papillary thyroid carcinoma.
7: Cancer research, 2009 Nov 24, 22(6)
Gonadotropin-Regulated Lymphangiogenesis in Ovarian Cancer Is Mediated by LEDGF-Induced Expression of VEGF-C.
[Abstract]The risk and severity of ovarian carcinoma, the leading cause of gynecologic malignancy death, are significantly elevated in postmenopausal women. Ovarian failure at menopause, associated with a reduction in estrogen secretion, results in an increase of the gonadotropic luteinizing hormone (LH) and follicle-stimulating hormone (FSH), suggesting a role for these hormones in facilitating the progression of ovarian carcinoma. The current study examined the influence of hormonal stimulation on lymphangiogenesis in ovarian cancer cells. In vitro stimulation of ES2 ovarian carcinoma cells with LH and FSH induced expression of vascular endothelial growth factor (VEGF)-C. In vivo, ovariectomy of mice resulted in activation of the VEGF-C promoter in ovarian carcinoma xenografts, increased VEGF-C mRNA level, and enhanced tumor lymphangiogenesis and angiogenesis. Seeking the molecular mechanism, we examined the role of lens epithelium-derived growth factor (LEDGF/p75) and the possible contribution of its putative target, a conserved stress-response element identified in silico in the VEGF-C promoter. Using chromatin immunoprecipitation, we showed that LEDGF/p75 indeed binds the VEGF-C promoter, and binding is augmented by FSH. A corresponding hormonally regulated increase in the LEDGF/p75 mRNA and protein levels was observed. Suppression of LEDGF/p75 expression using small interfering RNA, suppression of LH and FSH production using the gonadotropin-releasing hormone antagonist cetrorelix, or mutation of the conserved stress-response element suppressed the hormonally induced expression of VEGF-C. Overall, our data suggest a possible role for elevated gonadotropins in augmenting ovarian tumor lymphangiogenesis in postmenopausal women. [Cancer Res 2009;69(24):OF1-9].
8: Human pathology, 2009 Nov 12, 22(6)
Autocrine and paracrine roles of VEGF/VEGFR-2 and VEGF-C/VEGFR-3 signaling in angiosarcomas of the scalp and face.
[Abstract]Angiosarcoma of the skin is an extremely rare malignant tumor of vascular origin that usually arises in the scalp and face of elderly persons. To clarify its characteristic features and cell cycle kinetics, we quantitatively evaluated the expression of cell cycle-related molecules and vascular endothelial growth factors using immunohistochemical staining, for comparison with 2 benign vascular tumors of the skin, the capillary hemangioma and the cavernous hemangioma. Cell proliferation, determined with reference to the Ki-67 labeling index, was highest in angiosarcomas and lowest in cavernous hemangiomas (angiosarcomas versus capillary hemangioma, P = .014; capillary hemangioma versus cavernous hemangiomas, P = 1.4 x 10(-4)). Similar differences were also found in cyclin A, cyclin E, and p21(Waf1) expression. Expressions of cyclin D1 and p16(INK4A) were also significantly higher in angiosarcoma than in cavernous hemangioma. Expressions of these 5 proteins showed significant positive correlations with Ki-67 labeling indices (Spearman rho = 0.91-0.43). Expression levels of vascular endothelial growth factor and its receptor, VEGFR-2, were highest in angiosarcomas. VEGF-C expression in angiosarcomas was significantly higher than in cavernous hemangiomas, and its receptor VEGFR-3 expression was highest in angiosarcomas. Furthermore, significant positive correlations of these protein expression with Ki-67 labeling indices were noted (Spearman rho = 0.88-0.40). Among them, VEGFR-3 showed the highest correlation coefficient. These results suggest that not only VEGFR-2-mediated signal but also VEGFR-3-mediated signal may contribute to proliferation of vascular tumor cells as autocrine and paracrine signaling factors.
9: Development (Cambridge, England), 2009 Dec, 136(23)
Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries.
[Abstract]The development of arteries, veins and lymphatics from pre-existing vessels are intimately linked processes controlled by a number of well-studied reiteratively acting signalling pathways. To delineate the mechanisms governing vessel formation in vivo, we performed a forward genetic screen in zebrafish and isolated the mutant expando. Molecular characterisation revealed a loss-of-function mutation in the highly conserved kinase insert region of flt4. Consistent with previous reports, flt4 mutants were deficient in lymphatic vascular development. Recent studies have demonstrated a role for Flt4 in blood vessels and showed that Dll4 limits angiogenic potential by limiting Flt4 function in developing blood vessels. We found that arterial angiogenesis proceeded normally, yet the dll4 loss-of-function arterial hyperbranching phenotype was rescued, in flt4 signalling mutants. Furthermore, we found that the Flt4 ligand Vegfc drives arterial hyperbranching in the absence of dll4. Upon knockdown of dll4, intersegmental arteries were sensitised to increased vegfc levels and the overexpression of dll4 inhibited Vegfc/Flt4-dependent angiogenesis events. Taken together, these data demonstrate that dll4 functions to suppress the ability of developing intersegmental arteries to respond to Vegfc-driven Flt4 signalling in zebrafish. We propose that this mechanism contributes to the differential response of developing arteries and veins to a constant source of Vegfc present in the embryo during angiogenesis.
10: Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery, 2009 Jun, 23(12)
[Expression and significance of VEGF-C and VEGF-D in differentiated thyroid carcinoma]
[Abstract]OBJECTIVE: VEGF-C,D are known to be capable of inducing proliferation of lymphatic endothelia cell and development of lymphatic vessels, so we investigated the expression of VEGF-C,D in the differentiated thy roid carcinoma tissues microarray in order to understand the significance mechanism of cervix lymphatic metastasis of thyroid cancer. METHOD: A tissue microarray containing 71 specimens was constructed, including normal thyroid tissues, thyroid adenoma, papillary thyroid carcinoma with and without lymphatic metastasis, follicular thyroid carcinoma. VEGF-C, D protein expression was detected with immunohistochemistry. RESULT: The expression of VEGF-C,D were not observed in normal thyroid tissues and adenoma tissues. The expression of VEGF-C,D in pa pillary thyroid carcinoma was significantly higher than those in follicular thyroid carcinoma (P < 0.05) and adeno ma tissues (P < 0.01). The expression of VEGF-C,D in papillary thyroid carcinoma with lymphatic metastasis was significantly higher than those in papillary thyroid carcinoma without lymphatic metastasis (P < 0.05). CONCLUSION: By inducing proliferation of lymphatic endothelia cell and development of lymphatic vessels, VEGF-C,D contributed to lymphatic metastasis of papillary thyroid carcinoma.
11: Anatomical record (Hoboken, N.J. : 2007), 2009 May, 292(5)
Lentivirus-mediated small interfering RNA targeting VEGF-C inhibited tumor lymphangiogenesis and growth in breast carcinoma.
[Abstract]Lymph node metastasis is a major prognostic factor for patients with breast cancer. The activation of vascular endothelial growth factor (VEGF)-C plays a key role in lymph node metastasis through promoting lymphangiogenesis. Thus, we attempted to elucidate whether small interfering RNAs (siRNA) targeting VEGF-C could suppress lymphangiogenesis and lymph node metastasis in vivo. A lentivirus-based VEGF-C siRNA vector was infected into breast cancer cells and a xenograft model. The expression of VEGF-C mRNA and protein were quantified by quantitative real-time polymerase chain reaction (QRT-PCR), immunohistochemistry, and western blot analysis. The effect of VEGF-C siRNA on breast cancer cells was investigated by an invasion assay. Lymphangiogenesis was analyzed with anti-LYVE-1 and anti-D2-40 by immunohistochemical analysis. Lentivirus-mediated VEGF-C siRNA stably reduced VEGF-C mRNA and protein expression. VEGF-C siRNA inhibited the invasive ability of breast cancer cells in vitro. Five weeks after intratumoral injection, the tumor volume was significantly smaller in the VEGF-C siRNA group than in the control scramble siRNA group in the MDA-MB-231 cell xenograft model. The numbers of LYVE-1 and D2-40 positive vessels per microscopic field were significantly decreased in the VEGF-C siRNA group, which indicates that VEGF-C siRNA inhibited lymphangiogenesis. Moreover, lymph node metastasis was significantly suppressed by VEGF-C siRNA in vivo. In conclusion, these results indicate that lentivirus-mediated VEGF-C siRNA offers a new approach for therapeutic intervention to prevent tumor growth and lymphatic metastasis of breast cancer.
12: Leukemia & lymphoma, 2009 Mar, 50(3)
The prognostic significance of VEGF-C and VEGF-A in non-Hodgkin lymphomas.
[Abstract]Angiogenesis and lymphangiogensis are important in the proliferation and survival of the malignant hemeopoietic neoplasms. The aim of this study is to determine the prognostic role of angiogenesis and lymphangiogenesis in the development of lymphoma. For this aim, VEGF-A and VEGF-C were explored by immunohistochemistry in 177 cases. VEGF-C and VEGF-A were found to be positive in 34 and 61% of the samples. There was a good correlation between VEGF-C and VEGF-A expression (p = 0.0001). The clinical prognostic indicators were not significantly different between VEGF-C (+) and (-) and/or VEGF-A (+) and (-) cases. Overall survival (OS) rate was shorter in cases with VEGF-A (+) and VEGF-C (+) cases than with negative cases (p = 0.03 and p = 0.0005, respectively). The OS was significantly shorter in aggressive lymphomas expressing VEGF-A and VEGF-C but not in indolent lymphomas. The results of Cox regression analyses showed that VEGF-A and VEGF-C expressions are independent prognostic parameters (OR: 2.6, 95% CI: 1.3-5.0 for both (+) cases). In conclusion, VEGF-C and VEGF-A were positive in 34 and 61%, respectively, of the cases with NHL. The significant correlation between VEGF-C and VEGF-A suggests that lymphangiogenesis is important in the pathogenesis of lymphomas as shown in angiogenesis. The significantly shorter survival rates of VEGF-C and/or VEGF-A expressions indicate that angiogenesis and lymphangiogenesis are important in clinical outcome. Autocrine VEGF-A and VEGF-C crosstalks in lymphoma cells are important in lymphoma biology and inhibition of these signals with anti-angiogenic/anti-lymphangiogenic drugs and combination with chemo-immunotherapy regimens will be more useful in these cases.
13: Acta biochimica et biophysica Sinica, 2009 Mar, 41(3)
Prognostic significance of VEGF-C expression in correlation with COX-2, lymphatic microvessel density, and clinicopathologic characteristics in human non-small cell lung cancer.
[Abstract]Lung cancer is one of the most lethal cancers in China because of high incidence and high mortality. Cyclooxygenase-2 (COX-2) and vessel endothelial growth factor C (VEGF-C) were found to play an important role in lymphangiogenesis of malignant tumors. In this study, we investigated whether lymphatic microvessel density (LMVD) is related to the prognosis in non-small cell lung cancer (NSCLC) patients, and the expressions of COX-2 and VEGF-C so as to determine the possible role of COX-2 and VEGF-C in NSCLC lymphangiogenesis. Sixty-five formalin-fixed paraffin embedded tissue samples of NSCLC were evaluated for COX-2 and VEGF-C by immunohistochemical staining. To assess tumor lymphangiogenesis, LMVD was determined by immunohistochemical staining of VEGFR-3 polyclonal antibody. The relationship among COX-2 and VEGF-C expression, LMVD, and clinicopathologic parameters was analyzed. Among the 65 samples, high LMVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that LMVD value and lymph node metastasis were independent prognostic factors. The expression level of COX-2 and VEGF-C was significantly higher than those of the adjacent tissues. COX-2 and VEGF-C expressions in NSCLC significantly correlated with lymph node metastasis, but not with patient gender, age, tumor size, or tumor, nodes, metastasis classification stage. The mean LMVD value of COX-2- or VEGF-C-positive tumors was higher than that of COX-2- or VEGF-C-negative tumors. A significant correlation was found between the expressions of COX-2 and VEGF-C. This study suggests that LMVD may be one of the important prognostic factors for NSCLC patients. VEGF-C might play an important role in the COX-2 lymphangiogenic pathway. COX-2 and VEGF-C may play an important role in tumor progression by stimulating lymphangiogenesis. The inhibition of lymphangiogenesis, COX-2, or VEGF-C activity may have an important therapeutic benefit in the control of NSCLC.
14: Cancer biology & therapy, 2009 Apr, 8(8)
Expression of Tiam1 and VEGF-C correlates with lymphangiogenesis in human colorectal carcinoma.
[Abstract]OBJECTIVE: To investigate the relationship between Tiam1 and lymphangiogenesis in human colorectal carcinoma (CRC) tissues, as well as the expression of VEGF-C in a CRC cell line (HCT116) after knockdown of the Tiam1 gene with RNA interference (RNAi). RESULTS: In the specimens of CRC tissue, the positivity rate of Tiam1 and VEGF-C was 84% and 58%, respectively. The positivity rate of VEGF-C in the Tiam1 positive group (64.3%) was significantly higher than that in the Tiam1 negative group (25.0%). The LMVD in the Tiam1 positive group (11.35 +/- 3.34) was significantly higher than that in the Tiam1 negative group (7.38 +/- 2.27). In addition, the expression of the Tiam1 gene was efficiently blocked by RNAi. Downregulation of Tiam1 gene expression significantly suppressed HCT116 cell growth in vitro. Compared with untransfected HCT116 cells, HCT116 cells transfected with pGenesil-1-Tiam1 plasmids showed a significant decrease in the expression of VEGF-C. METHODS: The expressions of Tiam1, Rac1, VEGF-C and Podoplanin in 50 samples of CRC were detected by immunohistochemical analysis. The lymph microvessel density (LMVD) in Podoplanin positive specimens was evaluated. The results were analyzed statistically to investigate the correlation of Tiam1, VEGF-C, lymph node metastasis and other clinicopathological parameters. An shRNA eukaryotic expression vector against Tiam1 gene was constructed and transfected into HCT116 cells. The expression of Tiam1 gene was assessed by RT-PCR and western blot analysis. CONCLUSIONS: We suggest that the Tiam1 gene may act as a crucial therapeutic target for Lymphangiogenesis in CRC.
15: International journal of oncology, 2009 Mar, 34(3)
VEGF-C and VEGF-D expression is correlated with lymphatic vessel density and lymph node metastasis in oral squamous cell carcinoma: Implications for use as a prognostic marker.
[Abstract]The prognosis of patients with oral squamous cell carcinoma (SCC) is influenced by the presence of lymph node metastasis. In this study, we analyzed the relationship between lymphangiogenesis and the expression of VEGF-C and VEGF-D in association with lymph node metastasis in oral SCC. Oral SCC biopsy specimens (160 cases) were examined for lymphatic vessel density (LVD) and the expression of VEGF-C and VEGF-D immunohistochemically. The levels of VEGF-C and VEGF-D expression and LVD were significantly associated with lymph node metastasis (p<0.001). The expression of VEGF-C and VEGF-D increased the LVD significantly (p<0.001). Multivariate analysis showed that VEGF-C expression and LVD were significantly associated with lymph node metastasis (p<0.001). This study presents clinical evidence for the important roles of VEGF-C and VEGF-D in lymphangiogenesis and lymphatic metastasis of oral SCC, and suggests that VEGF-C or LVD can effectively predict lymphatic metastasis of oral SCC.
16: Virchows Archiv : an international journal of pathology, 2009 Mar, 454(3)
VEGF-C and VEGFR-3 in a series of lymphangiomas: Is superficial lymphangioma a true lymphangioma?
[Abstract]Lymphangiomas are commonly regarded as vascular malformations during embryonic development rather than as true neoplasms. VEGF-C and VEGFR-3 are known to be active in the formation of lymphangiomas. However, the significance of the disorders seems to be obscured by confusing different entities. In 114 lymphangiomas, we investigated the clinicopathological features and the expression of VEGF-C and VEGFR-3. The age of patients with lymphangioma circumscriptum or intraabdominal lymphangioma was significantly higher than in patients with cavernous lymphangioma and in patients with cystic hygroma. In cavernous lymphangioma, the age of female patients was significantly higher than in male patients. Five adult cystic hygromas were identified. VEGF-C was detected in 21 of 58 (36%) cavernous lymphangiomas, ten of 28 (36%) cystic hygromas, 0 of 12 (0%) lymphangioma circumscriptum, and four of ten (40%) intraabdominal lymphangiomas. VEGFR-3 was detected in 43 of 58 (72%) cavernous lymphangiomas, 20 of 28 (71%) cystic hygromas, six of 12 (50%) lymphangiomas circumscriptum, and seven of ten (70%) intraabdominal lymphangiomas. VEGF-C was absent from superficial lymphangiomas associated with cavernous lymphangiomas. In typical cases of cavernous lymphangioma, VEGF-C was strongly expressed, suggesting that these cases possessed proliferative activity. In cystic hygroma and intraabdominal lymphangioma, VEGF-C was limited in its distribution. Superficial lymphangiomas more likely represent from peripheral lymphatic dilatation rather than due to growth factor.
17: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban, 2008 Dec, 28(6)
Expression and clinical implication of HIF-1alpha and VEGF-C in non-small cell lung cancer.
[Abstract]To study the expression and implication of HIF-1alpha and VEGF-C in non-small cell lung cancer (NSCLC) and its relationship with clinical pathological features of NSCLC, immunohistochemical SP was used to detect the expression of HIF-1alpha and VEGF-C proteins in 48 NSCLC tissues and the same para-cancerous tissues. The positive rates of HIF-1alpha and VEGF-C were 70.8% (34/48) and 68.8% (33/48) respectively. The expression of HIF-1alpha protein was detected in a significantly greater proportion in NSCLC carcinoma tissues than that in para-cancerous tissues (12.5% and 16.7%, P<0.05). The positive rates of HIF-1alpha and VEGF-C were correlated with lymph node metastasis and TNM stage. No relationship was found between the two factors and age, sex, pathological subtypes and histological grades. The positive rates between HIF-1alpha and VEGF-C were correlated (P<0.05). HIF-1alpha and VEGF-C were over-expressed in NSCLC. They may be involved in the carcinogenesis of NSCLC, and play an important role in invasion and metastasis of NSCLC. HIF-1alpha and VEGF-C work synergically in the process of NSCLC.
18: Surgery, 2008 Dec, 144(6)
The potential clinical relevance of serum vascular endothelial growth factor (VEGF) and VEGF-C in recurrent papillary thyroid carcinoma.
[Abstract]BACKGROUND: Vascular endothelial growth factor (VEGF) promotes tumor angioinvasion while VEGF-C is a potent lymphangiogenic factor. This study aims at evaluating serum VEGF (sVEGF) and sVEGF-C levels in recurrent papillary thyroid carcinoma (PTC) patients. METHODS: Serum samples were collected preoperatively from 85 patients with primary PTC, 44 with benign thyroid diseases, and 19 with recurrent PTC. sVEGF and sVEGF-C levels were measured by enzyme-linked immunosorbent assay. RESULTS: Twelve patients had locoregional recurrence only while 7 patients had distant metastases, including 6 with concomitant or history of locoregional recurrence. Patients with recurrent PTC had significantly higher sVEGF (432 vs 263 pg/mL, P = .004) and sVEGF-C (6,433 vs 5,289 pg/mL, P = .006) levels than benign controls. sVEGF level was significantly elevated in patients with distant metastases compared with those of local recurrences only (580 vs 345 pg/mL, P = .037) while there was no significant difference of sVEGF-C level in both subgroup of patients. sVEGF, but not VEGF-C, showed a linear correlation with thyroglobulin levels in recurrent PTC patients. CONCLUSION: Both sVEGF and sVEGF-C levels are elevated in patients with recurrent PTC, and sVEGF distinguishes the presence of distant metastasis. Angiogenic markers should be further evaluated for their clinical relevance in monitoring and predicting the type of recurrence.
19: The Journal of investigative dermatology, 2009 May, 129(5)
Activation of the VEGFR-3 pathway by VEGF-C attenuates UVB-induced edema formation and skin inflammation by promoting lymphangiogenesis.
[Abstract]We have previously demonstrated that UVB irradiation resulted in impaired function of cutaneous lymphatic vessels, suggesting a crucial role of lymphatic function in the mediation of UVB-induced inflammation. Nonetheless, the molecular mechanisms of lymphatic involvement in inflammation have remained unclear. Here, we show that vascular endothelial growth factor (VEGF)-C expression is downregulated after UVB irradiation, associated with enlargement of lymphatic vessels and with an increase of macrophage infiltration in the dermis. To determine whether activation of VEGF-C/VEGFR-3 signaling might reduce UVB-induced inflammation, mice were exposed to a single dose of UVB irradiation together with intradermal injection of mutant VEGF-C (Cys156Ser), which specifically binds to VEGFR-3 on lymphatic endothelium. We found that the activation of VEGFR-3 attenuated UVB-induced edema formation, associated with a decreased number of CD11b-positive macrophages. Moreover, mutant VEGF-C injection inhibited UVB-induced enlargement of lymphatic vessels and also induced the proliferation of lymphatic endothelial cells. In contrast, treatment with mutant VEGF-C had no effect on blood vessel size or number. These results demonstrate that UVB-induced lymphatic impairment is mediated by downregulation of VEGF-C expression and that the activation of the VEGF-C/VEGFR-3 pathway might represent a feasible target for the prevention of UVB-induced inflammation by promoting lymphangiogenesis.