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Belleudi F, Cardinali G, Kovacs D, et al. KGF Promotes Paracrine Activation of the SCF/c-KIT Axis from Human Keratinocytes to Melanoma Cells. Transl Oncol. 2010;3(2):80-90doi: 10.1593/tlo.09196.
Belleudi, F., Cardinali, G., Kovacs, D., Picardo, M., & Torrisi, M. R. (2010). KGF Promotes Paracrine Activation of the SCF/c-KIT Axis from Human Keratinocytes to Melanoma Cells. Translational oncology, 3(2), 80-90. https://doi.org/10.1593/tlo.09196
Belleudi, Francesca, et al. "KGF Promotes Paracrine Activation of the SCF/c-KIT Axis from Human Keratinocytes to Melanoma Cells." Translational oncology vol. 3,2 (2010): 80-90. doi: https://doi.org/10.1593/tlo.09196
Belleudi F, Cardinali G, Kovacs D, Picardo M, Torrisi MR. KGF Promotes Paracrine Activation of the SCF/c-KIT Axis from Human Keratinocytes to Melanoma Cells. Transl Oncol. 2010 Apr;3(2):80-90. doi: 10.1593/tlo.09196. PMID: 20360932; PMCID: PMC2847315.
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Transl Oncol. 2010 Apr;3(2):80-90. doi: 10.1593/tlo.09196.

KGF Promotes Paracrine Activation of the SCF/c-KIT Axis from Human Keratinocytes to Melanoma Cells.

Translational oncology

Francesca Belleudi, Giorgia Cardinali, Daniela Kovacs, Mauro Picardo, Maria Rosaria Torrisi

Affiliations

  1. Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Medicina Clinica e Molecolare, Sapienza Università di Roma, Rome, Italy.

PMID: 20360932 PMCID: PMC2847315 DOI: 10.1593/tlo.09196

Abstract

The paracrine networks of the human melanoma microenvironment are able to influence tumor growth and progression. Among the paracrine growth factors involved in skin homeostasis, the KGF/FGF7 secreted by dermal fibroblasts promotes the epidermal proliferation and differentiation as well as the release from keratinocytes of other paracrine mediators. To evaluate the possible role played by KGF in affecting the behavior of different subtypes of melanoma carrying activating mutations or overexpression of the SCF receptor c-KIT, we used human melanoma cell lines, characterized by different expression levels of c-KIT and opposing responsivity to SCF, and HaCaT keratinocytes. Quantitative real-time reverse transcription-polymerase chain reaction assay and ELISA test on KGF-treated keratinocytes showed enhanced expression and secretion of SCF in response to KGF and dependent on functional KGF receptor. Immunofluorescence microscopy and biochemical analysis showed, in one of the selected melanoma cell models, SCF-dependent c-KIT activation induced by stimulation with the culture supernatants collected from KGF-treated keratinocytes. In keratinocyte-melanoma cocultures stained for the Ki67 proliferation marker, incubation with KGF induced enhanced growth not only of the keratinocytes but also of the melanoma cells, which could be blocked by the c-KIT inhibitor imatinib, demonstrating the establishment of a KGF-induced paracrine signaling network owing to the coexpression of biologically active SCF released from keratinocytes and functional c-KIT on melanoma cells.

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