INCREASED FIBRONECTIN-RECEPTOR EXPRESSION IN COLON CARCINOMA-DERIVED HT 29 CELLS DECREASES TUMORIGENICITY IN NUDE-MICE

Background/Aims: Following malignant transformation, epithelial cells of colorectal carcinomas, unlike normal colonic epithelial cells, no longer express the α5β1 fibronectin receptor. We hypothesized that the loss of α5β1 expression might facilitate the tumorigenicity of transformed colonic cells. Methods: To examine this hypothesis, we established subclones of the human colon adenocarcinoma cell line HT 29, which differ in their fibronectin receptor expression and tested their tumorigenicity in nude mice. Results: Our data indicate that the capacity to form tumors in nude mice after subcutaneous injection was significantly lower for α5-positive than for α5-negative cell clones. In addition, tumors from clones expressing no detectable levels of α5β1 grew rapidly, whereas tumors expressing elevated levels of fibronectin receptor grew slowly. Despite similar rates of adhesion to fibronectin for α5-positive and α5-negative cell clones in vitro, deposition of fibronectin in tumor-surrounding stroma was increased in tumors derived from α5-positive cells. Conclusions: Our results indicate that an increase of the α5β1-mediated interaction of malignant cells with the extracellular matrix may be responsible for decreased tumorigenicity of malignant transformed cells in colorectal carcinomas. © 1994 American Gastroenterological Association.