THE ROLE OF PLATELET-DERIVED GROWTH-FACTOR PRODUCTION BY TUMOR-ASSOCIATED MACROPHAGES IN TUMOR STROMA FORMATION IN LUNG-CANCER

Lung cancer is the most common cause of death by cancer in developed c ountries. Since a tumor cannot develop without the parallel expansion of a tumor stroma, a better understanding of its formation could lead to new therapeutical approaches. In this respect, since platelet-deriv ed growth-factor (PDGF) is a chemotactic and growth factor for mesench ymal and endothelial cells, lung tumors of patients undergoing surgery for nonsmall cell lung cancer were evaluated for their replication ra te using iododeoxyuridine incorporation, and for the expression of PDG F genes and the presence of PDGF A and B chains and of PDGF receptor a lpha and beta subunits. This observation demonstrates that: (a) tumor cells and stroma mesenchymal cells, but not tumor-associated macrophag es, display a high replication rate; (b) 1 of 3 tumors are characteriz ed by cancer cells expressing the genes for PDGF A and/or B chains, wh ile 1 of 2 tumors are composed of tumor cells presenting PDGF receptor s alpha and beta subunits on their surface, and in only 1 of 6 tumors, tumor cells coexpress PDGF and its receptor; (c) in almost all tumors , tumor-associated macrophages express PDGF A and/or B chain genes; (6 ) mesenchymal cells, as well as endothelial cells, do not express PDGF A and B chain genes but do express PDGF receptor alpha and beta subun its; and (e) an ongoing active process was suggested in the periphery of the tumor by the simultaneous strong expression of PDGF A and B cha in genes by tumor-associated macrophages and the high replication rate of mesenchymal and endothelial cells in the same area. Thus, PDGF is likely to have a limited autocrine role in tumor cell replication but is a potential player, in a paracrine fashion, in tumor stroma develop ment.