Chemotactic activity of bone and platelet-derived TGF-beta for bone-metastasizing rat Walker 256 carcinosarcoma cells

Bone is a major source of transforming growth factor-beta (TGF-beta), and a preferred target organ for metastasis of the rat Walker carcinosarcoma 256 (W256). Since chemotactic mechanisms may contribute to metastatic site specificity, we have tested the hypothesis that TGF-beta is a chemoattractant for these cancer cells. Purified platelet-derived TGF-beta elicited dose-dependent migration of W256 cells in the Boyden chamber assay with half-maximal responses (ED50) elicited by 0.12 +/- 0.01 ng TGF-beta/ml. Checkerboard analysis confirmed dependence of the response upon a concentration gradient. Conditioned media from organ cultures of bone contained TGF-beta and chemotactic activity in proportion to the extent of bone resorption. The chemotactic activity in conditioned bone culture medium and that of the purified platelet-derived TGF-beta were both inhibited after incubation with anti-TGF-beta 1. We conclude that TGF-beta, released from resorbing bone, can influence the migratory behavior of the osteotropic W256 cell line.