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Bcl-2 overexpression in melanoma cells increases tumor progression-associated properties and in vivo tumor growth

✍ Scribed by Daniela Trisciuoglio; Marianna Desideri; Ludovica Ciuffreda; Marcella Mottolese; Domenico Ribatti; Angelo Vacca; Mario Del Rosso; Lucia Marcocci; Gabriella Zupi; Donatella Del Bufalo

Book ID
102314165
Publisher
John Wiley and Sons
Year
2005
Tongue
English
Weight
408 KB
Volume
205
Category
Article
ISSN
0021-9541

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✦ Synopsis

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.

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