Paracrine angiogenic loop between head-and-neck squamous-cell carcinomas and macrophages.
Angiogenesis, an essential step in the development of neoplasia, is a complex process that involves the interaction of tumor cells with stromal cells. Tumor-associated macrophages (TAMs) can participate in the induction of tumor angiogenesis and are thought to be of prognostic value in some neoplasms. We have investigated how macrophages contribute to angiogenesis in head-and-neck squamous-cell carcinoma (HNSCC) and have found that tumor cells attract monocytes and activate them to secrete angiogenic factors. The attraction of macrophages was due to the secretion of monocyte chemotactic protein-1 and TGF-beta1 by tumor cells, while tumor production of TGF-beta1 was responsible for activating macrophages. In addition, activated macrophages produced cytokines that acted in a paracrine fashion by secreting both TNF-alpha and IL-1, which in turn stimulated tumor cells to secrete increased levels of IL-8 and VEGF. These data demonstrate that TAMs play an important role in the in vivo induction of angiogenesis in HNSCC and suggest that anti-angiogenic therapies for HNSCC and perhaps other neoplasms must include strategies that will block the ability of tumor cells to recruit macrophages into the tumor micro-environment.
Liss
C
C
Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA.
Fekete
M J
MJ
Hasina
R
R
Lam
C D
CD
Lingen
M W
MW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D018920:Coculture Techniques; D003315:Cornea / Q000098:blood supply; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D018919:Neovascularization, Physiologic; D011379:Prognosis; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D007375:Interleukin-1; D016209:Interleukin-8; D008222:Lymphokines; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors