title: Host-derived pericytes and Sca-1+ cells predominate in the MART-1- stroma fraction of experimentally induced melanoma.
abstract: Identification of cell types in tumor-associated stroma that are involved in the development of melanoma is hampered by their heterogeneity. The authors used flow cytometry and immunohistochemistry to demonstrate that anti-MART-1 antibodies can discriminate between melanoma and stroma cells. They investigated the cellular composition of the MART-1-, non-hematopoietic melanoma-associated stroma, finding it consisted mainly of Sca-1+ and CD146+ cells. These cell types were also observed in the skin and muscle adjacent to developing melanomas. The Sca-1+ cell population was observed distributed in the epidermis, hair follicle bulges, and tumor capsule. The CD146+ population was found distributed within the tumor, mainly associated with blood vessels in a perivascular location. In addition to a perivascular distribution, CD146+ cells expressed α-smooth muscle actin, lacked expression of endothelial markers CD31 and CD34, and were therefore identified as pericytes. Pericytes were found to be associated with CD31+ endothelial cells; however, some pericytes were also observed associated with CD31-, MART-1+ B16 melanoma cells that appeared to form blood vessel structures. Furthermore, the authors observed extensive nuclear expression of HIF-1α in melanoma and stroma cells, suggesting hypoxia is an important factor associated with the melanoma microenvironment and vascularization. The results suggest that pericytes and Sca-1+ stroma cells are important contributors to melanoma development.
authors.affiliation: BioImaging Laboratory, Program in Molecular Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: J Humberto
authors.initials: JH
authors.lastname: Treviño-Villarreal
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Cotanche
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sepúlveda
authors.forename: Magda E
authors.initials: ME
authors.lastname: Bortoni
authors.forename: Otto
authors.initials: O
authors.lastname: Manneberg
authors.forename: Taturo
authors.initials: T
authors.lastname: Udagawa
authors.forename: Rick A
authors.initials: RA
authors.lastname: Rogers
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D051929:CD146 Antigen / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D058965:MART-1 Antigen / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D020286:Pericytes / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism; D013997:Time Factors; D059016:Tumor Microenvironment
chemical_list: D000950:Antigens, Ly; D051929:CD146 Antigen; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C074650:Ly6a protein, mouse; D058965:MART-1 Antigen; C497903:Mcam protein, mouse; D008565:Membrane Proteins