Correlation of Vascular Endothelial Growth Factor-D Expression and VEGFR-3-Positive Vessel Density with Lymph Node Metastasis in Gastric Carcinoma

Choi, Jung Hye; Oh, Young Ha; Park, Yong Wook; Baik, Hong Kyu; Lee, Young Yiul; Kim, In Soon

doi:10.3346/jkms.2008.23.4.592

Cited by 25 publications

(19 citation statements)

References 25 publications

(26 reference statements)

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“…VEGFD was isolated as a cFos oncogene-inducible mitogen [27], and it is primarily found in skeletal muscle, heart, lung, and intestine [28]. More and more evidences proved that high VEGFD expression was related with tumor growth and metastasis [16][17][18][19][29][30][31]. In addition, there are some reports about the promotion of VEGFD on the tumor growth and metastasis of hepatocellular carcinoma [32,33].…”

Section: Discussionmentioning

confidence: 96%

Andrographolide decreased VEGFD expression in hepatoma cancer cells by inducing ubiquitin/proteasome-mediated cFos protein degradation

Zheng

Shi

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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Section: Discussionmentioning

confidence: 96%

Andrographolide decreased VEGFD expression in hepatoma cancer cells by inducing ubiquitin/proteasome-mediated cFos protein degradation

Zheng

Shi

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…VEGF-C not only induces the hyperplasia of peritumoral vessels, but also increases the volumetric flow rate of fluid in lymphatics that results in the increased delivery of tumor cells to the lymph node (44). Indeed, many other growth factors (FGF-2, Ang-1, VEGF-A, IGF-1, HGF) stimulate lymphangiogenesis indirectly through VEGF-C. VEGF-D also plays a role in the regulation of tumor lymphangiogenesis (45,46). Functional autocrine stimulation of VEGF-D in cancer not only stimulates the proliferation of cancer cells and LECs, but also plays a role in the maintenance of anti-apoptotic characteristics of tumor-derived endothelial cells (20).…”

Section: Discussionmentioning

confidence: 97%

Suppression of lymphangiogenesis in human lymphatic endothelial cells by simultaneously blocking VEGF-C and VEGF-D/VEGFR-3 with norcantharidin

Liu¹,

Qiu²,

Yuan³

et al. 2012

International Journal of Oncology

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Lymph node metastasis of tumors is a crucial early step in the metastatic process. Tumor lymphangiogenesis plays an important role in promoting tumor metastasis to regional lymph nodes. Norcantharidin (NCTD) has been reported to possess potent anti-angiogenesis and antitumor properties in several cell lines and xenograft tumor models. However, its role in tumor-associated lymphangiogenesis and lymphatic metastasis remains unclear. Here, we investigated the effect of NCTD on proliferation, apoptosis, migration, invasion and the lymphatic tube formation, lymphangiogenesis, of human lymphatic endothelial cells (HLECs) in vitro by MTT, proliferation assay, Hoechst staining and flow cytometry, scraping line method, Matrigel invasion assay, inverted or fluorescence microscope and transmission electron microscope. Moreover, the underlying mechanisms, such as VEGF-C, VEGF-D, VEGFR-3 at protein and mRNA levels in lymphangiogenesis using 3-dimensional (3-D) culture of HLECs were measured by immunohistochemistry, western blotting and real-time polymerase chain reaction (RT-PCR). It was shown that NCTD inhibited proliferation, migration, invasion and lymphatic tube formation (forming-lymphatic and/or formed-lymphatic) of HLECs, induced HLEC apoptosis (all P<0.01) significantly, in a dose- and time-dependent manner (IC50 6.8 µg/ml); and downregulated the expression of VEGF-C, VEGF-D and VEGFR-3 at protein or/and mRNA levels (P<0.01) in HLEC lymphatic tube formation. Thus, we identified for the first time that NCTD inhibited HLEC lymphangiogenesis by simultaneously blocking VEGF-C and VEGF-D/VEGFR-3 in vitro. The present findings may be of importance to explore the therapeutical target or strategy of NCTD for tumor lymphangiogenesis and lymphatic metastasis.

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“…An association of high LVD, rising regional and distant metastases, and poor patients’ survival was found for different types of tumours [8]. Further, the VEGF-C/VEGF-D/VEGFR-3 signalling axis was shown to induce metastatic spread [56], and a variety of human cancers revealed a correlation between high expression of VEGF-C, VEGF-D and/or VEGFR-3 and high LVD, lymph node metastasis and shortened survival [57,58,59]. In contrast, our findings did not show a correlation between the overall low LVD and expression levels of any VEGF or VEGFR, especially of VEGF-C, -D, and VEGFR-3, with systemic spread, or patients’ overall survival in ileal EC cell carcinoids.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factors, Angiogenesis, and Survival in Human Ileal Enterochromaffin Cell Carcinoids

Besig¹,

Voland²,

Baur³

et al. 2009

Neuroendocrinology

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Background and Aims: Well-differentiated neuro-endocrine ileal carcinoids are composed of serotonin-producing enterochromaffin (EC) cells. Life expectancy is determined by metastatic spread to the liver because medical treatment options are still very limited. Selective inhibition of angiogenesis or lymphangiogenesis might prevent tumour growth and metastatic spread. We examined the role of the vascular endothelial growth factors (VEGFs) A, B, C, D, and their receptors (VEGFRs) 1, 2, 3 in angiogenesis and lymphangiogenesis of ileal EC cell carcinoids with and without liver metastases. Methods: The expression of various VEGFs and VEGFRs was determined by quantitative real-time RT-PCR in healthy mucosa, primary tumour, lymph node metastases and liver metastases of 25 patients with ileal EC cell carcinoids. Microvessel density (MVD) was determined by CD-31 staining in primary tumours and lymphatic vessel density (LVD) by LYVE-1 staining. VEGF expression levels, MVD, LVD, and patients’ survival time were correlated using logistic regression and Kaplan-Meier survival analysis. Results: VEGF-A was highly expressed with no difference between normal mucosa and tumours. VEGF-B and -D as well as VEGFR-1 and -2 expression levels were significantly increased in the tumours when compared to normal mucosa. Patients with liver metastasis, however, had a significantly lower expression of the factors A, B, and C and the receptors 2 and 3. MVD in primary tumours positively correlated with the expression of VEGF ligands and their receptors, except for VEGF-D. LVD did not correlate with any VEGF ligand or receptor. Interestingly, low expression levels of VEGF-B were associated with poor survival. Conclusion: Patients with more aggressive metastatic spreading had relatively decreased expression levels of VEGF ligands and receptors. Thus, anti-angiogenic therapy may not be a suitable target in metastatic ileal EC cell carcinoids.

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Correlation of Vascular Endothelial Growth Factor-D Expression and VEGFR-3-Positive Vessel Density with Lymph Node Metastasis in Gastric Carcinoma

Cited by 25 publications

References 25 publications

Andrographolide decreased VEGFD expression in hepatoma cancer cells by inducing ubiquitin/proteasome-mediated cFos protein degradation

Andrographolide decreased VEGFD expression in hepatoma cancer cells by inducing ubiquitin/proteasome-mediated cFos protein degradation

Suppression of lymphangiogenesis in human lymphatic endothelial cells by simultaneously blocking VEGF-C and VEGF-D/VEGFR-3 with norcantharidin

Vascular Endothelial Growth Factors, Angiogenesis, and Survival in Human Ileal Enterochromaffin Cell Carcinoids

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