MODIFICATION OF PDGF-ALPHA RECEPTOR EXPRESSION OR FUNCTION ALTERS THEMETASTATIC PHENOTYPE OF 3LL CELLS

Functional PDGF alpha receptors are selectively expressed on highly lu ng-metastasizing clones of the 3LL Lewis lung carcinoma, but not on lo w-mestastatic clones. The highly metastatic clones are also growth ind uced in vitro by PDGF and lung conditioned medium. To investigate whet her modification of PDGF alpha receptor expression or function can aff ect metastatic capability, we transfected cells of a low-metastatic 3L L clone with a full length PDGF alpha receptor gene and cells of a hig hly-metastatic clone with a truncated kinase domain PDGF alpha recepto r gene. Introduction of the full length PDGF alpha receptor conferred upon low-metastatic cells the ability to grow in vitro in the presence of PDGF-AA and to colonize the lung in experimental and spontaneous m etastases assays. Conversely, introduction of a truncated version of t he PDGF alpha receptor into highly metastatic cells reduced their meta static load to control levels. Accordingly, their responses to PDGF-AA , including growth stimulation and receptor autophosphorylation, were reduced. These results demonstrate that PDGF alpha receptor expression and function can control the capacity of tumor cells to generate meta stases in the lung. The response of this receptor to lung-derived PDGF -like factors may define a paracrine mode of metastatic cell growth in the target organ.