Correlation between colon cell oligosaccharides progressive alteration, cellular colonigenicity in soft agar and metastatic ability.

Earlier studies showed that the extracellular matrix and the conditioned medium from colon carcinoma support and catalyze the conversion of normal epithelial to colon carcinoma cells (14, 16). Since the cause of this apparent change in malignant potential is completely unknown, the following experiments examined molecular changes accompanying and mediating the transition. Colon epithelial cell cultures were initiated from normal colon biopsies. The cell cultures were carried on in standard medium on fibronectin-coated plates, and in conditioned medium on extracellular matrix from confirmed colon carcinoma. At time intervals, during 12 months period, aliquots were harvested, transferred into roller bottles to obtain enough cells to isolate cellular Poly(A)+-enriched RNA, cell membrane oligosaccharides and to determine cellular growth characteristics. During the 12 months in vitro culture, normal colon epithelial (NCE) cells grown on fibronectin in the standard growth medium maintained their initial characteristics. Whereas, NCE cells grown on the extracellular matrix and in colon carcinoma conditioned medium, progressively acquired the ability to form colonies in soft agar, to form tumors when implanted subcutaneously and to metastasize into the liver when administered intravenously into athymic mice. Poly(A)+-enriched RNA from NCE cells grown on fibronectin and in standard culture medium, did not, whereas the RNA from NCE cells grown on the extracellular matrix and in the colon carcinoma conditioned medium hybridized with 32P-cDNA from colon carcinoma. There were significant changes in the composition and profile of the oligosaccharides from membranes of NCE cells grown on the extracellular matrix. There was significant correlation (P less than 0.001) between the last characteristics.