Protein expression of melanocyte growth factors (bFGF, SCF) and their receptors (FGFR‐1, c‐kit) in nevi and melanoma

Abstract

Protein expression of melanocyte growth factors (bFGF, SCF) and their receptors (FGFR-1, c-kit) in nevi and melanoma Background: Basic fibroblast growth factor (bFGF) and stem cell factor (SCF) are essential growth factors for melanocytes which carry the receptors FGFR-1 for bFGF and c-kit for SCF. Because both factors may be involved in melanoma development, the expression of bFGF/FGFR-1 and SCF/c-kit was investigated in melanocytic tumors of different progression stages. Methods: Fifty primary melanomas and 44 melanocytic nevi were analyzed for the expression of SCF, c-kit, bFGF, and FGFR-1 by immunohistochemistry. Results: In melanoma, SCF and c-kit were expressed in 76 and 84%, respectively, and coexpressed in 66%. bFGF and FGFR-1 were expressed in 45 and 86%, respectively, and coexpressed in 46%. In melanocytic nevi, SCF was expressed in 23% and c-kit in 70% while coexpression was more common in dysplastic (39%) than nondysplastic subtypes (8%). bFGF and FGFR-1 were expressed in 55 and 67%, respectively, while coexpression was found in 47% but varied considerably between different histological subtypes. Conclusions: SCF and c-kit were frequently expressed by melanomas and dysplastic nevi suggesting an autocrine growth mechanism as described for bFGF. In both nevi and melanoma, c-kit was almost exclusively found in the epidermis while bFGF was more common in the dermis. Thus the growth factor/receptor expression seems to depend on the cutaneous localization of the melanocytic tumors. Basic fibroblast growth factor (bFGF) and stem cell factor (SCF) belong to the most important growth factors for melanocytes that carry the receptors FGFR-1 for bFGF and c-kit for SCF. Both factors may be involved in melanoma development as shown recently.1 The dependence of melanocytes on exogeneous growth factors produced by keratinocytes and fibroblasts is lost in melanoma cells in favor of an autonomous production of a whole variety of different growth factors and cytokines such as platelet derived growth factor (PDGF), bFGF, hepatocyte growth factor (HGF), and interleukin-8 (IL-8).One of the most potent growth factors in melanoma is bFGF, also called FGF-2. bFGF is one of 23 members of the FGF gene family known to modulate cell growth, differentiation, motility, and angiogenesis. 2,3 Four different molecular isoforms of bFGF (18,22,23, and 24 kDa) have been described, representing alternative translation products from a single

Analysis of c-KIT expression and KIT gene mutation in human mucosal melanomas

“…The numbers of positively labelled melanoma cells were scored as follows: 0 for less than 10% positive cells, 1 ( þ ) for 10 -25% positive cells, 2 ( þ þ ) for 26 -50% positive cells, 3 ( þ þ þ ) for 51 -75% and 4 ( þ þ þ þ ) for 76 -100% positive cells. We did not differentiate between cytoplasmatic and membranous staining as we did not observe isolated surface staining and earlier studies showed cytoplasmatic staining along with membranous staining in melanoma cells positive for c-KIT (Pereira et al, 2005;Giehl et al, 2007;Rivera et al, 2008).…”

Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function

“…SCF expression has been demonstrated in a number of human primary tumors (eg, melanoma, pancreatic cancer, colorectal carcinoma) [60][61][62][63][64] and can potentially be exploited for cancer treatment. Our studies demonstrate the feasibility and applicability of targeting the SCF/ckit pathway to prevent and revert immune tolerance mediated by MDSCs in mice with large tumor burdens.…”

Leukemic Cells Create Bone Marrow Niches That Disrupt the Behavior of Normal Hematopoietic Progenitor Cells

“…SCF is produced by a wide variety of solid tumors (23)(24)(25)(26). AML cell lines and primary AML cells have been shown to produce SCF RNA transcripts, but expression of SCF by hematologic malignancies is not well defined (27).…”