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 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.
Vignaud
J M
JM
Département d'Anatomie Pathologique, Université de Nancy, France.
Marie
B
B
Klein
N
N
Plénat
F
F
Pech
M
M
Borrelly
J
J
Martinet
N
N
Duprez
A
A
Martinet
Y
Y
D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D008264:Macrophages / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000032:analysis*; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis*; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology
D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor