Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes

Abstract

Human tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase-polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7, gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1 alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)-alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40 chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF), basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.

In contrast to their murine counterparts, normal human keratinocytes and human epidermoid cell lines A431 and HaCaT fail to express IL-10 mRNA and protein

“…RT-PCR analysis of pure NHK, melanocytes, Langerhans cells and fibroblast suspensions provided conclusive proof that within normal epidermis only melanocytes were able to synthesize IL-10 mRNA. Our finding that melanocytes express IL-10 mRNA is in agreement with the observation of other investigators [45,46]. We and others [45] could not detect IL-10 protein in the supernatants of normal human melanocytes.…”

Low-Level Monocyte Chemoattractant Protein-1 Stimulation of Monocytes Leads to Tumor Formation in Nontumorigenic Melanoma Cells

“…In vitro, only a few melanoma cell lines express TNF-␣ RNA transcripts (55). Therefore, the source of the TNF-␣ increase observed in this study may be due to the activation of monocytes through contact with SBcl2 cells or indirectly through soluble factors.…”

Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase

“…As a nonspecific acute phase response to almost all forms of inflammation (Pepys, 1995), CRP is synthesised in hepatocytes in response to cytokines such as mainly interleukin-6 (Il-6; Moshage et al, 1988;Castell et al, 1989;Kishimoto, 1989;Klein et al, 1991;Hirano, 1992). As melanoma cells are known to produce Il-6 (Colombo et al, 1992;Lee et al, 1992;Lu and Kerbel 1993;Mattei et al, 1994;Francis et al, 1996), serum CRP might reflect Il-6 production from the tumour. However, tumour-specific immune interaction with T cells, macrophages or monocytes might also be responsible for elevated Il-6 levels, as these cell are known to produce this cytokine, too.…”