Vascular endothelial growth factor-A and -C: expression and correlations with lymphatic metastasis and prognosis in colorectal cancer

Abstract

Previous studies obtained contradicting results regarding the correlation between expression of VEGF-A, VEGF-C and colorectal cancer patients' clinicopathological features and prognosis. Moreover, the association between the growth factors' expression and lymphatic vessel invasion (LVI) with intratumoral and peritumoral difference has not been reported. In this study, 81 primary colorectal cancer samples were immunohistochemically stained for VEGF-A, VEGF-C and podoplanin. The expression of VEGF-A and VEGF-C in marginal portion was significantly higher than those in central portion (P = 0.000 for both). The expression of VEGF-A in marginal portion was correlated with lymph node metastasis (P = 0.031). The expression of VEGF-C in marginal portion was correlated with TNM stage (P = 0.045), peritumoral LVI (P = 0.048) and lymph node metastasis (P = 0.019). The group with high VEGF-A expression in marginal portion showed worse survival than the low expression group (P = 0.039). Patients with high expression of VEGF-C in the marginal portion were not significantly different from those with low VEGF-C expression (P = 0.121). Patients with high expression of both VEGF-A and VEGF-C in the marginal portion showed the worst survival (P = 0.015). In conclusion, increased expression of VEGF-A and VEGF-C in marginal portion of colorectal cancer was correlated with lymph node metastasis. VEGF-C facilitates colorectal cancer cells invade into peritumoral lymphatic vessels, and different mechanisms may exist in the invasion of tumor cells into peritumoral and intratumoral lymphatic vessels. Assessment the expression of both VEGF-A and VEGF-C in the marginal portion of tumor may help to identify patients with colorectal cancer with unfavourable overall survival.

Molecular Mechanisms of Lymphatic Metastasis

“…In fact, the results of some studies showed that the expression levels of VEGF-D and VEGFR-3 in colorectal carcinoma tissues are significantly higher than in normal tissues (Omachi, Kawai et al 2007). Furthermore, recent reports have linked the VEGF-C/VEGF-D expression to lymphatic metastasis and poor patient outcome (Nagahashi, Ramachandran et al 2010;Lin, Lin et al 2011). Our histopathological examination also revealed that VEGF-C was present in CRC tissue, whereas the surrounding tissue was negative.…”

Analysis of colorectal cancer morphology in relation to sex, age, location, and family history

“…RKIP has recently been characterized as a metastasis suppressor gene and loss of it has been associated with an increased frequency of distant metastases in CRC [44]. The expression of vascular endothelial growth factor C (VEGF-C) in CRC has been linked to lymphatic vessel invasion, probably by VEGF-C promoting the dilatation of lymphatic vessels and thereby facilitating the invasion of cancer cells [45]. All in all, these findings may speak for a difference between sporadic and familial CRCs in the expression of proteins facilitating vascular invasion, but immunohistochemical comparison of the two groups is required.…”

Dihydroartemisinin inhibits tumor growth of human osteosarcoma cells by suppressing Wnt/β-catenin signaling

“…MMP9, member of the MMP family, is capable of degrading extracellular matrix and is involved in the metastasis of cancer (35,36). VEGF is a key angiogenic factor that can stimulate vasculogenesis and angiogenesis (37)(38)(39). Cancer that expresses VEGF is prone to invade and metastasize (38,39), and downregulation of VEGF can attenuate the invasiveness phenotype of malignant tumor (40,41).…”

“…VEGF is a key angiogenic factor that can stimulate vasculogenesis and angiogenesis (37)(38)(39). Cancer that expresses VEGF is prone to invade and metastasize (38,39), and downregulation of VEGF can attenuate the invasiveness phenotype of malignant tumor (40,41). COX2 is known to be closely associated with tumor growth and metastasis in several types of human tumors (42,43,25).…”