Skip to main content

Advertisement

Log in

Stem cell factor affects tumour progression markers in metastatic melanoma cells

  • Original Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Stem cell factor (SCF), next to various relevant biological effects exerted on many cell types, is able to keep melanocyte homeostasis through its receptor c-kit. Only a minority of metastatic melanoma cells (MMC) express c-kit receptor, but c-kit positive MMC move more slowly towards tumour progression and have a more natural tendency to undergo apoptosis. In our study c-kit positive MMC from human melanoma metastases and a c-kit positive human melanoma cell line—SK-MEL-28—showed a clear-cut reduction of cytokines normally up-regulated along melanoma progression after SCF stimulation. SCF was also able to maintain all MMC and SK-MEL-28 cells in a well differentiated status with an increase in organellogenesis and in particular of melanosomes in various degree of differentiation, but it did not induce apoptosis as observed in other in vitro models. The increase of melanosomes matched an increase of tyrosinase production. SCF did not modify the expression of NOS while it enhanced the expression of HLA-DR molecules on MMC membranes. Taken altogether these data stress the biological activity of SCF as a cytokine which is able to maintain MMC in a well differentiated status, and suggest a more in depth evaluation of possible effects of SCF on melanoma cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

SCF:

Stem cell factor

MMC:

Metastatic melanoma cells

GM-CSF:

Granulocyte-monocyte colony stimulating factor

TGF-β:

Transforming growth factor-β

TNF-α:

Tumour necrosis factor-α

IL-6:

Interleukin-6

IL-7:

Interleukin-7

IL-8:

Interleukin-8

IL-10:

Inteleukin-10

EM:

Electron microscopy

References

  1. Martin FH, Suggs SV, Langley KE et al (1990) Primary structure and functional expression of rat and human stem cell factor DNAs. Cell 63:203–211

    Article  PubMed  CAS  Google Scholar 

  2. Anderson DM, Lyman SD, Baird A et al (1990) Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell 63:235–243

    Article  PubMed  CAS  Google Scholar 

  3. Andrews RG, Knitter GH, Bartelmez SH et al (1991) Recombinant human stem cell factor, a c-kit ligand, stimulates hematopoiesis in primates. Blood 78:1975–1980

    PubMed  CAS  Google Scholar 

  4. Huang E, Nocka K, Beier DR et al (1990) The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 63:225–233

    Article  PubMed  CAS  Google Scholar 

  5. Zsebo KM, Williams DA, Geissler EN et al (1990) Stem cell factor is encoded at the S1 locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 63:213–224

    Article  PubMed  CAS  Google Scholar 

  6. Herlyn M, Berking C, Li G, Satyamoorthy K (2000) Lessons from melanocyte development for understanding the biological events in naevus and melanoma formation. Melanoma Res 10:303–312

    Article  PubMed  CAS  Google Scholar 

  7. Prignano F, Gerlini, Fossombroni V et al (2001) Control of the differentiation state and function of human epidermal Langerhans cells by cytokines in vitro. EADV J 15:433–440

    CAS  Google Scholar 

  8. Kunisada T, Yoshida H, Yamazaki H et al (1998) Transgene expression of steel factor in the basal layer of epidermis promotes survival, proliferation, differentiation and migration of melanocyte precursors. Development 125:2915–2923

    PubMed  CAS  Google Scholar 

  9. Grichnick JM, Burch JA, Burchette J, Shea CR (1998) The SCF/KIT pathway plays a critical role in the control of normal human melanocyte homeostasis. J Invest Dermatol 111:233–238

    Article  Google Scholar 

  10. Natali PG, Nicotra MR, Winkler AB et al (1992) Progression of human cutaneous melanoma is associated with loss of expression of c.kit proto-oncogene receptor. Int J Cancer 52:197–201

    PubMed  CAS  Google Scholar 

  11. Lassam N, Bickford S (1992) Loss of c-kit expression in cultured melanoma cells. Oncogene 7:51–56

    PubMed  CAS  Google Scholar 

  12. Huang S, Luca M, Gutman M et al (1996) Enforced C-KIT expression renders highly metastatic human melanoma cells susceptible to stem cell factor-induced apoptosis and inhibits their tumorigenic and metastatic potential. Oncogene 13:2339–2347

    PubMed  CAS  Google Scholar 

  13. Prignano F, Coronnello M, Pimpinelli N et al (2002) Immunophenotypical markers, ultrastructure and chemosensitivity profile of metastatic melanoma cells. Cancer Lett 186:183–192

    Article  PubMed  CAS  Google Scholar 

  14. Haass NK, Herlyn M (2005) Normal human melanocyte homeostasis as a paradigm for understanding melanoma. J␣Invest Dermatol Symp Proc 10:153–163

    Article  CAS  Google Scholar 

  15. Shih IM, Herlyn M (1994) Autocrine and paracrine roles for growth factors in melanoma. In vivo 8:113–124

    PubMed  CAS  Google Scholar 

  16. Moretti S, Pinzi C, Spallanzani A et al (1999) Immunohistochemical evidence of cytokine networks during progression of human melanocytic lesions. Int J Cancer (Pred Oncol) 84:160–168

    Article  CAS  Google Scholar 

  17. Rodeck U (1993) Growth factor independence and growth regulatory pathways in human melanoma development. Cancer Met Rev 12:219–226

    Article  CAS  Google Scholar 

  18. Papadimitrou CA, Topp MS, Serve H et al (1995) Recombinant human stem cell factor does exert minor stimulation of growth in small cell lung cancer and melanoma cell lines. Eur J Cancer 31A(13–14):2371–2378

    Article  Google Scholar 

  19. Mattei S, Colombo MP, Melani C et al (1994) Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. Int J Cancer 56:853–857

    PubMed  CAS  Google Scholar 

  20. Yue YF, Dummer R, Geertsen R et al (1997) Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules. Int J Cancer 71:630–637

    Article  PubMed  CAS  Google Scholar 

  21. Xu W, Liu LZ, Loizidou M et al (2002) The role of nitric oxide in cancer. Cell Res 12:311–320

    Article  PubMed  Google Scholar 

  22. Massi D, Franchi A, Sardi I et al (2001) Inducible nitric oxide synthase expression in benign and malignant cutaneous melanocytic lesions. J Pathol 194:194–200

    Article  PubMed  CAS  Google Scholar 

  23. Nyormoi O, Bar-Eli M (2003) Transcriptional regulation of metastasis-related genes in human melanoma. Clin Exp Metast 20:251–263

    Article  CAS  Google Scholar 

  24. Andalib AR, Lawry J, Ali SA et al (1997) Cytokine modulation of antigen expression in human melanoma cell lines derived from primary and metastatic tumour tissues. Melanoma Res 7:32–42

    Article  PubMed  CAS  Google Scholar 

  25. Schadendorf D, Moller A, Algermissen B et al (1993) IL-8 produced by human malignant cells in vitro is an essential autocrine factor. J Immunol 151:2667–2675

    PubMed  CAS  Google Scholar 

  26. Moncada S, Palmer MJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology and pharmacology. Pharm Rev 43:109–142

    PubMed  CAS  Google Scholar 

  27. Ahmed B, Van Den Oord JJ (2000) Expression of the inducible isoform of nitric oxide synthase in pigment cell lesions of the skin. Br J Dermatol 143:432–440

    Article  Google Scholar 

  28. Dong Z, Staroselsky AH, Qi X et al (1994) Inverse correlation between expression of inducible nitric oxide synthase activity and production of metastasis in K-1735 murine melanoma cells. Cancer Res 54:789–793

    PubMed  CAS  Google Scholar 

  29. Fecker LF, Eberle J, Orfanos CE, Geilen CC (2002) Inducible nitric oxide synthase is expressed in normal human melanocytes but not in melanoma cells in response to tumor necrosis factor-α, Interferon-γ and lipopolysaccharide. J Invest Dermatol 118:1019–1025

    Article  PubMed  CAS  Google Scholar 

  30. Tang CH, Grimm EA (2004) Depletion of endogenous nitric oxide enhances cis-platin induced apoptosis in a p53-dependent manner in melanoma cell lines. J Bio Chem 279(1):288–298

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Silvia Moretti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prignano, F., Gerlini, G., Salvatori, B. et al. Stem cell factor affects tumour progression markers in metastatic melanoma cells. Clin Exp Metastasis 23, 177–186 (2006). https://doi.org/10.1007/s10585-006-9027-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-006-9027-9

Keywords

Navigation