Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer.
ABSTRACT Vascular endothelial growth factor-C (VEGF-C) is a specific ligand which induces lymphangiogenesis. We examined the expression of VEGF-C protein to determine its role in the progression of breast cancer. Immunohistochemical analysis revealed that VEGF-C was overexpressed in 39 of 98 breast cancer specimens (39.8%) but not in adjacent normal mammary glands. The expression of VEGF-C showed a significant correlation with lymphatic vessel invasion (p = 0.0004). It is noteworthy that the 5-year disease free survival rate of the VEGF-C positive group was significantly poorer than that of negative group (p = 0.0356). We suggest that as expression of VEGF-C is not implicated in lymphatic spread, it may prove to be a promising marker to predict the recurrence of breast cancer.
- SourceAvailable from: ncbi.nlm.nih.gov[show abstract] [hide abstract]
ABSTRACT: The growth of solid tumors is dependent on angiogenesis, the formation of new blood vessels. Vascular endothelial growth factor (VEGF) is a secreted endothelial-cell-specific mitogen. We have recently characterized two novel endothelial growth factors with structural homology to VEGF and named them VEGF-B and VEGF-C. To further define the roles of VEGF-B and VEGF-C, we have studied their expression in a variety of human tumors, both malignant and benign. VEGF-B mRNA was detected in most of the tumor samples studied, and the mRNA and the protein product were localized to tumor cells. Endothelial cells of tumor vessels were also immunoreactive for VEGF-B, probably representing the binding sites of the VEGF-B polypeptide secreted by adjacent tumor cells. VEGF-C mRNA was detected in approximately one-half of the cancers analyzed. Via in situ hybridization, VEGF-C mRNA was also localized to tumor cells. All lymphomas studied contained low levels of VEGF-C mRNA, possibly reflecting the cell-specific pattern of expression of the VEGF-C gene in the corresponding normal cells. The expression of VEGF-C is associated with the development of lymphatic vessels, and VEGF-C could be an important factor regulating the mutual paracrine relationships between tumor cells and lymphatic endothelial cells. Furthermore, VEGF-C and VEGF-B can, similarly to VEGF, be involved in tumor angiogenesis.American Journal Of Pathology 08/1998; 153(1):103-8. · 4.52 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Vascular endothelial growth factor-C (VEGF-C) functions specifically to induce lymphangiogenesis. We examined the relationship between expression of VEGF-C and clinicopathological features in patients with colorectal cancer. The expression of VEGF-C in the 99 primary tumours and 18 metastatic lymph nodes from colorectal cancer patients was examined immunohistochemically. To verify VEGF-C mRNA expression, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out. The expression of VEGF-C correlated with lymphatic involvement, lymph nodes metastasis, and depth of invasion. On the other hand, correlations were nil with regard to gender of the patients, histologic type, venous involvement, and liver metastasis. The expression of VEGF-C in metastatic lymph nodes was fairly consistent with this expression in the primary tumour. Survival time was shorter for VEGF-C positive groups than for VEGF-C negative ones, but with no statistically significant difference. RT-PCR findings revealed that the expression of VEGF-C mRNA correlated mostly with that of VEGF-C protein expression. VEGF-C may play an important role in lymphatic spread of colorectal cancer.British Journal of Cancer 11/2000; 83(7):887-91. · 5.08 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Our analyses in several different tumor settings challenge the prevailing view that malignancies and metastases generally initiate as avascular masses that only belatedly induce vascular support. Instead, we find that malignant cells rapidly co-opt existing host vessels to form an initially well-vascularized tumor mass. Paradoxically, the co-opted vasculature does not undergo angiogenesis to support the growing tumor, but instead regresses (perhaps as part of a normal host defense mechanism) via a process that involves disruption of endothelial cell/smooth muscle cell interactions and endothelial cell apoptosis. This vessel regression in turn results in necrosis within the central part of the tumor. However, robust angiogenesis is initiated at the tumor margin, rescuing the surviving tumor and supporting further growth. The expression patterns of Angiopoietin-2 (the natural antagonist for the angiogenic Tie2 receptor) and vascular endothelial growth factor (VEGF) strongly implicate these factors in the above processes. Angiopoietin-2 is highly induced in co-opted vessels, prior to VEGF induction in the adjacent tumor cells, providing perhaps the earliest marker of tumor vasculature and apparently marking the co-opted vessels for regression. Subsequently, VEGF upregulation coincident with Angiopoietin-2 expression at the tumor periphery is associated with robust angiogenesis. Thus, in tumors, Angiopoietin-2 and VEGF seem to reprise the roles they play during vascular remodeling in normal tissues, acting to regulate the previously underappreciated balance between vascular regression and growth.Oncogene 10/1999; 18(38):5356-62. · 7.36 Impact Factor