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 and ß 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 and ß 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 and ß 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. 1 This work was supported in part by grants from Ligue Française contre le Cancer (Comités de Meurthe et Moselle, Moselle et Meuse), Association pour la Recherche sur le Cancer, and Fondation Médicale pour la Recherche. 2 To whom requests for reprints should be addressed.