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Disrupted Communication between Late-Stage Premalignant Human Colon Epithelial Cells by 12-O-Tetradecanoylphorbol-13-acetate

Department of Gastrointestinal Cancer Research, Memorial Sloan-Kettering Cancer Center, New York 10021 [E. A. F.], and Department of Pathology, New York University Medical School, New York, New York 10016 [M. S.]

Premalignant epithelial cells derived from benign tumors of the human colon fall into three classes based on the properties of the cultured cells and the pathology and clinical prognosis of the tumors themselves. Cellular communication was compared by injection of fluorescein into single cells in primary cultures of late- and early-stage premalignant cells, in primary cultures of colon adenocarcinomas, and in cultures of a tumorigenic established human colon carcinoma cell line. Many cells in both types of premalignant cultures appeared highly coupled inasmuch as the dye was often detected in several cells adjacent to the injection site. Thus, most premalignant cells within a colony were in communication with the surrounding cells. In contrast, many malignant cells were uncoupled and passed dye to few, if any, neighboring cells. The tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate caused extensive uncoupling of cells in late-stage premalignant cultures, while not eliminating the extensively coupled areas found in early-stage premalignant cultures. 12-O-Tetradecanoyl-phorbol-13-acetate had no effect on coupling between tumorigenic cells from an established carcinoma cell line which were already extensively uncoupled. Tumor promoters may play an important role in the transition of late-stage premalignant cells to malignancy by decreasing intercellular communication between premalignant cells at this specific stage in tumor development.

¹ Recipient of National Cancer Institute Grant R26 CA 28822 from the National Large Bowel Cancer Project. To whom requests for reprints should be addressed.

² Recipient of National Cancer Institute Grant CA 27869.

Received 2/ 9/82. Accepted 8/23/82.