Host-Derived Pericytes and Sca-1+ Cells Predominate in the MART-1- Stroma Fraction of Experimentally Induced Melanoma

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, CD1468(+) cells expressed alpha-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-1 alpha 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. (J Histochem Cytochem 59: 1060-1075, 2011)