title: Expression of cyclo-oxygenase-2 in macrophages associated with cutaneous melanoma at different stages of progression.
abstract: The biological significance of the almost constant presence of macrophages in the tumoral microenvironment is an issue debated by several authors. The major difficulty in understanding the role played by tumor-associated macrophages (TAMs) in tumor progression is due to the contrasting effects of TAMs found in different studies. In addition, there is a limited information on which of the many biological activities expressed by TAMs are critical in inducing stimulatory or inhibitory effect on tumor growth. The aim of our study was: (a) to explore to what extent cyclo-oxygenase-2 (COX-2) in TAMs associated with human melanoma is expressed at different stages of tumor progression; and (b) to explore whether COX-2 expression in TAMs is stimulated by melanoma cells. In order to answer this question, we determined COX-2 positive TAMs associated with cutaneous melanocytic nevi, in situ, invasive and metastatic melanoma. In addition, we investigated whether COX-2 is expressed in peritoneal thioglycollate-elicited macrophages after co-cultivation with murine B16 melanoma cells. We found that COX-2-positive TAMs, as revealed by immunohistochemical analysis, were rare in common nevi and "dysplastic nevi", but present in a high percentage in in situ and thin melanoma. COX-2-positive TAMs were also found in more advanced tumors and metastatic melanoma, although at a significantly lower percentage in these latter. The in vitro protocol revealed that COX-2 was expressed in peritoneal macrophages upon contact with B16 murine melanoma cells, but not with normal murine fibroblasts. On the whole, the results of in vivo and in vitro studies suggest that COX-2 expressed in TAMs appears to act as an effective biomarker of melanoma progression, and melanoma cells themselves might stimulate COX-2 in macrophages.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Florence, Viale G.B. Morgagni 50, I-50134 Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchini
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Chiara
authors.initials: C
authors.lastname: Marconi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Franchi
authors.forename: Gianna
authors.initials: G
authors.lastname: Baroni
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
authors.forename: Antonella
authors.initials: A
authors.lastname: Mannini
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mugnai
authors.forename: Lido
authors.initials: L
authors.lastname: Calorini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009506:Nevus / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D013864:Thioglycolates / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D013864:Thioglycolates; D051546:Cyclooxygenase 2