Alterations in the extracellular matrix organization associated with the reexpression of tumorigenicity in human cell hybrids

Abstract

The expression of fibronectin on the cell surface was evaluated on a series of intraspecific human cell hybrids formed between HeLa [human cervical carcinoma cells] and normal fibroblast strains. Although these hybrids continued to express many of the in vitro transformation properties of their corresponding tumorigenic HeLa parent, they were unable to form tumors when inoculated into athymic nude mice. From these suppressed hybrid populations, rare tumorigenic segregant subpopulations arose which had regained their tumorigenic capacity. A comparison of the expression of fibronectin on the cell surface was made between these tumorigenic segregant cell lines and their corresponding non-tumorigenic HeLa/fibroblast hybrid. A striking alteration in the cell surface organization was observed to correspond with the reexpression of tumorigenicity in these hybrids. Tumorigenic HeLa/fibroblast hybrids were significantly altered in their cellular and colonial morphology. Surface fibronectin and collagen displayed an extensive degree of codistribution and expressed a coordinate shift in organization which correlated with the appearance of tumorigenic segregant hybrid populations. These observations are in agreement with the apparently close structural association between fibronectin and collagen and suggest that the organization of these 2 components in the extracellular matrix may be an important determinant for in vivo growth potential.