Defective basal lamina formation by transformed mammary epithelial cells: a reduced effect of collagen on basal lamina (heparan sulfate-rich) proteoglycan degradation.

Invasive, spontaneously transformed mammary epithelial cells derived from the normal NMuMG cell line have lost the ability of their parental cells to respond in vitro to the presence of a collagen substratum by forming a continuous glycosaminoglycan (GAG)-rich basal lamina. On collagen, the cells synthesize 35S-GAG at the same rates, but the transformed cells accumulate less 35S-GAG than the normal cells because a larger fraction of their newly synthesized 35S-GAG is rapidly degraded. Chromatography of the 35SO4-containing materials from cultures on collagen indicates that the reduced accumulation of 35S-GAG by the transformed cells reflects less of a heparan sulfate-rich proteoglycan fraction which has been found in the basal lamina. On plastic substrata, however, the normal and transformed cells have near identical rates of 35S-GAG synthesis and degradation and they accumulate similar low amounts of the basal lamina proteoglycan fraction, which is rapidly degraded. Thus, transformation appears to impair the ability of the cells to reduce basal lamina proteoglycan degradation in response to collagen. This impairment may prevent the neoplastic cells from forming a complete basal lamina and, therefore, allow local invasion.