1. Bcl-2 overexpression in melanoma cells increases tumor progression-associated properties and in vivo tumor growth.
- Author
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Trisciuoglio, Daniela, Desideri, Marianna, Ciuffreda, Ludovica, Mottolese, Marcella, Ribatti, Domenico, Vacca, Angelo, Del Rosso, Mario, Marcocci, Lucia, Zupi, Gabriella, and Del Bufalo, Donatella
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CANCER cells , *MELANOMA , *CELL lines , *METALLOPROTEINASES , *TUMOR growth , *PHENOTYPES , *CANCER invasiveness - Abstract
In this study, we demonstrated that bcl-2 overexpression in human melanoma cells consistently enhanced the activity of multiple metastasis-related proteinases, in vitro cell invasion, and in vivo tumor growth. In particular, by using the M14 parental cell line, the MN8 control clone, and two bcl-2 overexpressing derivatives, we found that bcl-2 overexpressing cells exposed to hypoxia, when compared to parental cells, expressed higher level of several metalloproteases (MMPs) such as MMP-2, MMP-7, MT1-MMP, and tissue inhibitors of metalloproteases-1 and -2. Moreover, bcl-2 overexpression in melanoma cells enhanced in vitro invasion on matrigel and, in vivo tumor growth. The more aggressive behavior of bcl-2 transfectants tumors is significantly associated to an increase in MMP-2 expression as well as in a more elevated microvessel density as compared to the parental line. Taken together, our data suggest that bcl-2 plays a pivotal role in the regulation of molecules associated with the migratory and invasive phenotype, contributing, in cooperation to hypoxia, to tumor progression. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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