A tumor-specific membrane phosphoprotein marker in human cell hybrids.
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Biomedical subjects
Publications and source records attributed to C J Der.
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The expression of fibronectin on the cell surface was evaluated on a series of intraspecific human cell hybrids formed between HeLa 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 now 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. Following specific immunofluorescent staining for fibronectin, 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 also significantly altered in both their cellular and colonial morphology. Double immunofluorescent staining to simultaneously visualize both surface fibronectin and collagen revealed that these two extracellular matrix proteins 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 two components in the extracellular matrix may be an important determinant for in vivo growth potential.
An analysis of the correlation between tumorigenicity and the loss of expression of the large external transformation-sensitive glycoprotein (LETS) was performed on human cell hybrids and their respective normal and tumorigenic parental cell lines. The distribution of cell surface LETS protein in a series of cell lines was examined by both specific immunofluorescent staining and by gel electrophoresis of lactoperoxidase-catalyzed, iodinated cell surface proteins. The tumorigenicity of these cell lines was assayed in nude mice. Although the series of cell lines studied provided a broad spectrum of LETS protein expression, both quantitatively and qualitatively, there does not appear to be a correlation between tumorigenicity and decreased expression of the LETS protein. In a series of transformed, nontumorigenic hybrids, the LETS protein expression was found to be altered with respect to both decreased organizational complexity and decreased content. These hybrids continue to express a number of other transformed phenotypes. Conversely, a number of tumorigenic hybrids continue to express relatively high levels of LETS protein when compared with nontumorigenic hybrids. Thus an alteration in LETS protein expression by itself, or in concert with a spectrum of other transformation properties, does not appear to be a sufficient requirement for tumorigenicity and lends further support to an apparent separate control of the transformed versus tumorigenic phenotype.