Host-derived pericytes and Sca-1+ cells predominate in the MART-1- stroma fraction of experimentally induced melanoma |
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Authors: | J Humberto Trevi?o-Villarreal Douglas A Cotanche Rosalinda Sepúlveda Magda E Bortoni Otto Manneberg Taturo Udagawa Rick A Rogers |
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Institution: | BioImaging Laboratory, Program in Molecular Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA. |
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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. |
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Keywords: | MART-1 Sca-1 CD146 pericytes melanoma tumor-associated stroma |
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