The level of the expression of TEM-1, TEM-7, TEM-7R and TEM-8 (but not TEM-2 and TEM-6) were associated with both nodal involvement and disease progression, and may therefore, have a prognostic value in colorectal cancer.
Tumour angiogenesis is a critical step in the growth, metastatic spread and regrowth of colorectal cancer. Angiogenesis specific to tumour is a complicated process, the mechanisms of which remain unclear. Metastasis of colorectal cancer may result from passive entry into the circulation secondary to the effect of angiogenic factors. The survival and growth of colorectal tumour and thus their metastases are dependent on the balance of endogenous angiogenic and anti-angiogenic factors such that the outcome favours increased angiogenesis. Angiogenesis has become an attractive target for anticancer drug development, based on its important roles in tumour growth, invasion and metastasis. Several growth factors have been identified that regulate angiogenesis in colorectal cancer; the most important of these are vascular endothelial growth factors (VEGF), and of the several angiogenic factors, VEGF expression at the deepest invasive site of tumour is the most statistically significant prognostic indicator in advanced colorectal carcinoma. In this review article, we provide an overview on angiogenic factors and their receptors, and discuss the role of newly identified tumour endothelial markers (TEMs) that are involved in tumour-associated angiogenesis in colorectal cancer.
Tumour endothelial marker-8 (TEM-8) belongs to a family of endothelial markers that are raised during tumour angiogenesis. We have recently reported aberrant expression of TEMs at the mRNA level in human breast cancer. This study sought to examine the level of TEM-8 expression at the protein and mRNA level in human breast cancer tissue, and in a panel of human breast cancer cell lines. We also wished to determine if TEM-8 can be used as a suitable marker for identifying tumour associated micro-vessels. At the mRNA level more tumours showed positive TEM-8 expression compared to normal background tissue. TEM-8 was detected in a variety of breast cancer cell lines, endothelial cells (HECV) and in a human fibroblast cell line (MRC5) at both the mRNA and protein level. Using immunohistochemistry the distribution of TEM-8 staining was more widespread in invasive breast cancer tissue compared to normal background tissue. Furthermore, the TEM-8 marker was found to be more discriminatory in identifying micro-vessels in tumour endothelium (2.8±0.83 vs. normal 1.66±0.52; P<0.011), compared to the vWFA marker (1.61±0.54 vs. normal 2.71±0.76; P<0.009). Raised levels of TEM-8 were associated with shorter survival outcome, but were not correlated to disease-free survival as shown by Kaplan-Meier and Cox regression analysis. We conclude that TEM-8 is a useful marker for identifying tumour associated micro-vessels and that elevated levels are associated with disease progression, which may have some bearing on the prognostic outcome in breast cancer.
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