Adhesion, chemotaxis, and aggregation of Walker carcinosarcoma cells in response to products of resorbing bone.

Cells from the Walker 256 carcinosarcoma, a rat breast tumor with a propensity to metastasize to bone, were labeled with [131I]5-iodo-2'-deoxyuridine and then added to 96-hour organ cultures of fetal Sprague-Dawley rat calvaria that had been prelabeled with 45Ca and incubated with various stimulators or inhibitors of resorption. In conditioned media from resorbing bone cultures, the number of cells that attached to the bone surfaces correlated with the degree of bone resorption (r = 0.65; P less than .005). The attachment response was maximal after 180 minutes of cocultivation and was inhibited by preincubation of the tumor cells with 10(-5) M cytochalasin B. Cellular attachment appeared to be promoted by a trypsin-sensitive factor released into the organ culture medium from resorbing bones. Enhanced tumor cell attachment did not appear to be related to a change in the surface properties of the resorbing bone, since it was not observed when the conditioned media were replaced with fresh medium. Furthermore, tumor cells placed in conditioned medium demonstrated increased attachment to plastic surfaces and formed aggregates. While there was a direct correlation between the ability of conditioned medium to promote cellular adhesion and chemotactic migration (r = 0.85; P less than .05), the factors responsible for chemotaxis and adhesion could be separated by gel filtration. The release of such factors from resorbing bones may promote the formation of secondary bone tumors, since in this system attachment of unlabeled cells was followed by proliferation of tumor cells and evidence of bone invasion.