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Oncogene. 2010 Nov 18;29(46):6115-24. doi: 10.1038/onc.2010.350. Epub 2010 Aug 23.

Tenascin-C promotes melanoma progression by maintaining the ABCB5-positive side population.

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  • 1Molecular and Cellular Oncogenesis Program, Division of Molecular and Cellular Biology, The Wistar Institute, Philadelphia, PA 19104, USA.

Abstract

Tenascin-C (TNC) is highly expressed in melanoma; however, little is known about its functions. Recent studies indicate that TNC has a role within the stem cell niche. We hypothesized that TNC creates a specific environment for melanoma cells to show a stem cell-like phenotype, promoting tumor growth and evading conventional therapies. TNC expression was strongly upregulated in melanoma cells grown as 3D spheres (enriched for stem-like cells) when compared to adherent cells. Downmodulation of TNC by shRNA lentiviruses significantly decreased the growth of melanoma spheres. The incidence of pulmonary metastases after intravenous injection of TNC knockdown cells was significantly lower in NOD/SCID IL2Rγ(null) mice compared with control cells. Melanoma spheres contain an increased number of side population (SP) cells, which show stem cell characteristics, and have the potential for drug resistance due to their high efflux capacity. Knockdown of TNC dramatically decreased the SP fraction in melanoma spheres and lowered their resistance to doxorubicin treatment, likely because of the downregulation of multiple ATP-binding cassette (ABC) transporters, including ABCB5. These data suggest that TNC is critical in melanoma progression as it mediates protective signals in the therapy-resistant population of melanoma.

PMID:
20729912
[PubMed - indexed for MEDLINE]
PMCID:
PMC2991494
Free PMC Article

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