The role of platelet-derived growth factor production by tumor-associated macrophages in tumor stroma formation in lung cancer.

Abstract

Lung cancer is the most common cause of death by cancer in developed countries. 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-derived growth-factor (PDGF) is a chemotactic and growth factor for mesenchymal and endothelial cells, lung tumors of patients undergoing surgery for non-small cell lung cancer were evaluated for their replication rate using iododeoxyuridine incorporation, and for the expression of PDGF genes and the presence of PDGF A and B chains and of PDGF receptor alpha and beta subunits. This observation demonstrates that: (a) tumor cells and stroma mesenchymal cells, but not tumor-associated macrophages, display a high replication rate; (b) 1 of 3 tumors are characterized by cancer cells expressing the genes for PDGF A and/or B chains, while 1 of 2 tumors are composed of tumor cells presenting PDGF receptors 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; (d) mesenchymal cells, as well as endothelial cells, do not express PDGF A and B chain genes but do express PDGF receptor alpha and beta subunits; and (e) an ongoing active process was suggested in the periphery of the tumor by the simultaneous strong expression of PDGF A and B chain 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 development.