ESTABLISHMENT OF PRIMARY CULTURES FROM HUMAN COLONIC TISSUE DURING TUMOR PROGRESSION - VITAMIN-D RESPONSES AND VITAMIN-D-RECEPTOR EXPRESSION

Primary cultures derived from pre-cancerous and cancerous human colon tissue are essential for understanding normal and abnormal growth func tion in the large intestine. Here presented are (i) the methodology fo r routine establishment of primary cultures of normal, adenoma-and car cinoma-derived cells, and (ii) data for the apparently protective role of vitamin-D compounds in colon carcinogenesis. The steroid hormone 1 ,25-dihydroxyvitamin D3 and some non-hypercalcemic analogs reduce the high mitotic rate of adenoma cells to that of normal colonocytes. Afte r vitamin-D treatment, tumor cells ave less proliferative and differen tiation is enhanced. Primary-colon-cancer cultures display a mosaic pa ttern of vitamin-D-receptor expression, at the mRNA level and at the p rotein level, with varying intensity of expression in positive cells, This suggests that, in human colorectal tumors in vivo, a large fracti on of cells will respond to genomic action of vitamin-D compounds. (C) 1998 Wiley-Liss, Inc.