Melanotransferrin induces human melanoma SK-Mel-28 cell invasion in vivo
- Laboratoire de Medecine Moleculaire, Service d'Hemato-Oncologie-Hopital Ste-Justine/BIomed-Universite du Quebec a Montreal, Montreal, Que., H3C 3P8 (Canada)
The expression of melanotransferrin (MTf), a membrane-bound glycoprotein highly expressed in melanomas, is correlated with tumor vascularization and progression, suggesting a proinvasive function associated with MTf in malignant tumors. To test this hypothesis, we silenced MTf in human melanoma SK-MEL-28 cells using small interfering RNA (siRNA) and examined the plasmin activity and invasiveness of MTf-silenced melanoma. In vitro, the siRNA-mediated MTf knockdown inhibited by 58% the cell surface activation of plasminogen into plasmin. In addition, decreased expression of MTf in melanoma cells reduced cell migration. In vivo, we used a nude mice invasion model in which tissue factor (TF) induces vascular [{sup 125}I]-fibrin deposition following injection. Using this metastasis model, the invasive potential of MTf-silenced cells into the lungs was reduced by fivefold. Altogether, these findings strongly suggest that MTf overexpression in melanoma cells contributes to tumor progession by stimulating plasmin generation as well as cell migration and invasion.
- OSTI ID:
- 20979789
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 353, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2006.12.034; PII: S0006-291X(06)02687-8; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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