Expression of the vascular endothelial growth factor receptor 3 (VEGFR-3/FLT4) in human colorectal adenocarcinoma

Witte, Deborah; Carlson, Nicole; Ali, Najeeba; Younes, Mamoun

doi:10.1016/s0016-5085(00)85216-6

Cited by 41 publications

(57 citation statements)

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“…Upregulation of cytoplasmic VEGFR3 protein expression has been demonstrated immunohistochemically in colorectal cancer tissue specimens and increased expression was associated with poorer overall survival (Po0.05) (Witte et al, 2002). This again demonstrates the potent paracrine nature of the interaction between the cytokines and their receptor in the microenvironment of the tumour.…”

Section: Colorectal Cancermentioning

confidence: 73%

Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy

Duff

Jeziorska

et al. 2003

Br J Cancer

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Section: Colorectal Cancermentioning

confidence: 73%

Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy

Duff

Jeziorska

et al. 2003

Br J Cancer

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“…An increasing number of studies have shown the expression of VEGFR-3 on tumor cells in human cancer patients (5,(17)(18)(19)(21)(22). However, this phenomenon has never been reported in mouse tumor models.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, coexpression of VEGFR-3 with VEGFC in human cancer cells was associated with increased metastasis and poorer survival, suggesting a possible autocrine loop between VEGFC and VEGFR-3 in cancer cells (21,22).…”

Section: Introductionmentioning

confidence: 99%

SAR131675, a Potent and Selective VEGFR-3–TK Inhibitor with Antilymphangiogenic, Antitumoral, and Antimetastatic Activities

Alam

Blanc

Gueguen-Dorbes

et al. 2012

Molecular Cancer Therapeutics

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SAR131675 is a potent and selective VEGFR-3 inhibitor. It inhibited VEGFR-3 tyrosine kinase activity and VEGFR-3 autophosphorylation in HEK cells with IC 50 values of 20 and 45 nmol/L, respectively. SAR131675 dose dependently inhibited the proliferation of primary human lymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC 50 of about 20 nmol/L. SAR131675 was found to be highly selective for VEGFR-3 versus 107 receptors, enzymes, ion channels, and 65 kinases. However, it was moderately active on VEGFR-2 with a VEGFR-3/VEGFR-2 ratio of about 10. SAR131675 had no antiproliferative activity on a panel of 30 tumors and primary cells, further showing its high specificity and indicating that SAR131675 is not a cytotoxic or cytostatic agent. SAR131675 was very well tolerated in mice and showed a potent antitumoral effect in several orthotopic and syngenic models, including mammary 4T1 carcinoma and RIP1.Tag2 tumors. Interestingly, it significantly reduced lymph node invasion and lung metastasis, showing its antilymphangiogenic activity in vivo. Moreover, treatment of mice before resection of 4T1 primary tumors was sufficient to prevent metastasis. Tumor-associated macrophages (TAM) play an important role in tumor growth and metastasis. The expression of VEGFR-3 on TAMs has been recently described. F4/80 immunostaining clearly showed that SAR131675 significantly reduced TAM infiltration and aggregation in 4T1 tumors. Taken together, SAR131675 is the first highly specific VEGFR-3-TK inhibitor described to date, displaying significant antitumoral and antimetastatic activities in vivo through inhibition of lymphangiogenesis and TAM invasion.

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“…Vascular endothelial growth factor-C has been detected in many human cancers, and a number of reports have shown a correlation between VEGF-C expression in human tumours and the formation of metastases in regional lymph nodes. So far, the VEGF-C levels in several types of primary tumours have correlated significantly with lymph node metastasis (Akagi et al, 2000;Hashimoto et al, 2001;Witte et al, 2002;Juttner et al, 2006;Su et al, 2006). However, there are also some reports did not find a correlation between VEGF-C expression and metastasis (Gunningham et al, 2000;George et al, 2001;Komuro et al, 2001;Hanrahan et al, 2003;Koyama et al, 2003).…”

Section: The Vegf-c/vegfr-3 Axis Affects Tumour Progression By Regulamentioning

confidence: 99%

“…Recent studies have indicated that VEGFR-3, which has been proposed as a marker for lymphatic endothelial cells, is also expressed in a variety of human malignancies. Vascular endothelial growth factor receptor 3 expression in colon cancer has been associated with poorer survival, suggesting an axis between VEGF-C and VEGFR-3 in colorectal cancer (Witte et al, 2002). Expression of VEGFR-3 has also been reported to be significantly correlated with the different stages of cervical carcinogenesis (Van Trappen et al, 2003).…”

mentioning

confidence: 99%

The role of the VEGF-C/VEGFR-3 axis in cancer progression

et al. 2006

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Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR-3) (also called VEGFR-3) is activated by its specific ligand, VEGF-C, which promotes cancer progression. The VEGF-C/VEGFR-3 axis is expressed not only by lymphatic endothelial cells but also by a variety of human tumour cells. Activation of the VEGF-C/VEGFR-3 axis in lymphatic endothelial cells can facilitate metastasis by increasing the formation of lymphatic vessels (lymphangiogenesis) within and around tumours. The VEGF-C/VEGFR-3 axis plays a critical role in leukaemic cell proliferation, survival, and resistance to chemotherapy. Moreover, activation of the VEGF-C/VEGFR-3 axis in several types of solid tumours enhances cancer cell mobility and invasion capabilities, promoting cancer cell metastasis. In this review, we discuss the novel function and molecular mechanism of the VEGF-C/VEGFR-3 axis in cancer progression.

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Expression of the vascular endothelial growth factor receptor 3 (VEGFR-3/FLT4) in human colorectal adenocarcinoma

Cited by 41 publications

References 0 publications

Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy

Vascular endothelial growth factors C and D and lymphangiogenesis in gastrointestinal tract malignancy

SAR131675, a Potent and Selective VEGFR-3–TK Inhibitor with Antilymphangiogenic, Antitumoral, and Antimetastatic Activities

The role of the VEGF-C/VEGFR-3 axis in cancer progression

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