EXPRESSION OF FIBRONECTIN ED-A(-B+ ISOFORMS BY HUMAN AND EXPERIMENTALCOLORECTAL-CANCER - CONTRIBUTION OF CANCER-CELLS AND TUMOR-ASSOCIATEDMYOFIBROBLASTS() AND ED)

Alternative splicing of primary fibronectin (FN) mRNA results in the s ynthesis of different isoforms. ED-A(+) and ED-B+ FN isoforms are abse nt from plasma FN and are representative of cellular FN. Their express ion was studied in human and rat normal colon, in human colorectal car cinomas, and in transplanted tumors derived from a chemically-induced rat colon cancer. In normal colon, only the ED-A(+) FN isoform was exp ressed as a thin deposit between crypt colonocytes and pericryptal myo fibroblasts. Conversely, heavy ED-A(+) FN deposits and lighter ED-B+ F N expression were found in the stroma of colorectal tumors in associat ion with myofibroblasts surrounding tumor glands. Some colonic cancer cells also contained intracellular FN isoform granules and expressed F N mRNA. Tumor-associated myofibroblasts and some cancer cell lines wer e able to synthesize and deposit extracellular ED-A(+) and ED-B+ FN in vitro. FN isoform deposition by tumor-associated myofibroblasts was n ot modulated by colon cancer cell-conditioned medium, but was strongly enhanced when myofibroblasts were cultured on colon cancer cell extra cellular matrix or on laminin. These results show that eht ED-A(+) and ED-B+ FN isoforms were overexpressed in colorectal cancer. Cancer cel ls can deposit these FN isoforms directly and also stimulate their dep osition by tumor-associated myofibroblasts.