Expression of functionally intact PDGF-alpha receptors in highly metastatic 3LL Lewis lung carcinoma cells

The ability of disseminating tumor cells to grow in a target organ is the final limiting step of the metastatic cascade. The growth of a highly lung-metastatic clone, D122, of the murine 3LL Lewis lung carcinoma was induced in vitro with lung-conditioned media (CM) to a greater extent than that of a weakly metastatic clone, A9. With the use of platelet-derived growth factor (PDGF)-alpha-receptor-specific antibodies, the possible paracrine mode of metastatic cell growth was further suggested by demonstrating the presence of these receptors on highly metastatic cells only. Receptors for PDGF have been found almost exclusively on cells of mesenchymal and glial origin. Therefore, the functionality of this receptor in the D122 epithelial cell line was verified by immune complex kinase and ligand-stimulation assays. Moreover, PDGF was shown to specifically induce in vitro growth of D122 highly metastatic cells only and to be abundantly expressed in lung CM but not in kidney or liver CM. Thus, the interaction of PDGF-like factors in the lung with PDGF receptors on the metastatic tumor cell may be important in the development of metastatic lesions in the target organ.