These data indicate that VEGF is a commonly expressed angiogenic factor in human colorectal cancer metastases, that VEGF receptors are up-regulated as a concomitant of hepatic tumorigenesis, and that modulation of VEGF gene expression or activity may represent a potentially effective antineoplastic therapy in colorectal cancer.
VEGF, flt, and KDR expression was localized by in situ hybridization and immunohistochemistry in frozen sections of primary tumors from five patients with ovarian carcinoma and from metastases of ovarian carcinoma from three different patients.
Considerable evidence is gathering for the involvement of vascular endothelial growth factor (VEGF) in the vascularization and growth of primary tumours as well as in the formation of metastases.
Thus, the vascular endothelial growth factor-signaling system seems to be an appropriate target for inhibition of tumor angiogenesis and metastasis formation.
This is the first report that progestins regulate VEGF expression in human breast cancer cells and raises the possibility that increased angiogenesis in response to endogenous progesterone or its therapeutically used analogues may play a role in cell growth or metastasis in a subset of human breast tumors.
It was also found that increasing TF expression in human melanoma cells does not increase expression of vascular endothelial growth factor or promote growth and vascularization of tumors derived from the melanoma cells, suggesting that TF acts by a mechanism other than angiogenesis to promote metastasis.
The basic carcinogenic processes are: (1) constitutive prostaglandin biosynthesis and formation of mutagenic oxygen and nitrogen free radicals responsible for tumor initiation; (2) PGE-2-induced expression of aromatase and constitutive estrogen biosynthesis which sustains mitogenesis and tumor promotion; and (3) PGE-2-induced expression of vascular endothelial growth factor which stimulates angiogenesis and tumor metastasis.
Concerning the functional significance of VEGF receptor expression, VEGF treatment of VEGFR-1-expressing tumor cells induced the inhibition of cell proliferation by 25 to 55% and the inhibition of tumor cell migration by 29 to 55%.
Its expression in sarcoma cells was reported to up-regulate the vascular endothelial growth factor (VEGF) gene and thereby enhance tumor angiogenesis, which is essential to tumor metastasis.
Both platelet-derived endothelial cell growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) are known to promote the development of new blood vessels, which are fundamental to tumor growth and metastasis.
This study was designed to more directly establish the role of VEGF in the growth and metastasis of human colon cancer using a genetically engineered cancer cell line.
Because the crucial role of angiogenesis has been demonstrated in tumor growth and metastasis, the present study was undertaken to characterize the relative expression of vascular endothelial growth factors VEGF (vascular endothelial growth factor), VEGF-B, VEGF-C, and their receptors KDR (kinase insert domain-containing receptor), FLT-1 (fms-like tyrosine kinase), and FLT-4 in human colonic cancers, in relation to the Astler-Coller pathological classification, and to prognosis.
Circulating VEGF was derived from HCC tissue. sVEGF concentrations could be a new marker for predicting the angiogenesis, invasion and metastasis of HCC.
Vascular endothelial growth factor (VEGF), the most potent angiogenic factor identified to date, is associated with growth and metastasis of solid tumours, including melanoma.
Taken together, these data represent the first demonstration that synthetic ribozymes targeting VEGF receptor mRNA reduced the growth and metastasis of solid tumors in vivo.
These results support the hypothesis that two VEGF family members are involved in lymph node metastasis at two distinct steps; VEGF-C facilitates entry of cancer cells into the lymph vasculature, whereas VEGF-A promotes the growth of metastatic tumor through angiogenesis.