Intravasation-related metastatic factors in colorectal cancer

Alterations in adhesion molecules, angiogenesis, and matrix metalloproteinases have been associated with metastasis and intravasation. The present study investigated the role of these metastatic factors in the context of primary colorectal tumor. Intravasated colorectal epithelial cells were detected by an RT-PCR assay, and the expression of E-cadherin, alpha-catenin, or beta-catenin as well as the vascularity of tumor were assessed by immunohistochemical staining. Activity of matrix metalloproteinase was assessed by gelatin zymography. The tumor venous blood was positive for guanylyl cyclase C (GCC) mRNA expression in 40 of 68 patients, but alteration in expression of E-cadherin, alpha-catenin, or beta-catenin was not significantly associated with the presence of colorectal epithelial cells in paired portal venous blood. Further, matrix metalloproteinase activity did not correlate with the presence of intravasated colorectal epithelial cells. Multivariate analysis demonstrated that the only factor associated with intravasated colorectal tumor cells was the vascularity of the tumor. Thus, metastasis of colon cancer may result from passive entry into the circulation secondary to angiogenic factors and does not appear to involve other metastatic factors studied in our experiments.