Cell-line-dependent inhibition of phenotypic expression of preneoplastic and neoplastic tracheal epithelial cells by normal tracheal cells in denuded tracheal transplants.

Abstract

The inhibitory role of normal cells on the expression of neoplastic or preneoplastic cells was investigated using repopulated, heterotopic tracheal transplants. Denuded tracheal transplants were repopulated with a constant number of cells composed of different ratios of normal and neoplastic or preneoplastic rat tracheal epithelial (RTE) cells. Tracheas were harvested at 2 and 6 weeks after implantation, and examined histologically and in cell culture for the presence of the abnormal cells. Two neoplastic cell lines showed marked differences in the number and extent of squamous cell carcinomas which developed in tracheas repopulated at equivalent ratios of RTE: neoplastic cells. One preneoplastic cell line was almost completely inhibited in proliferative and phenotypic expression by normal cells, in contrast to a marked lack of suppression by normal cells of a second preneoplastic cell line. The extent of squamous metaplasia present, or the presence of invasive squamous cell carcinoma, was dependent upon the cell line instilled, suggesting that the cell lines represent different stages in the progression toward neoplasia. The lack of inhibition of some tumorigenic or preneoplastic cells by normal cells in this study is in conflict with previously published reports which indicate that the presence of greater than 10(4) normal cells are capable of inhibiting neoplastic expression in this model. Based on these studies, it appears that the nature of the neoplastic or preneoplastic cell is critical in determining whether inhibition by normal cells can occur.