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Bcl‐2 overexpression in melanoma cells increases tumor progression‐associated properties and in vivo tumor growth
Author(s) -
Trisciuoglio Daniela,
Desideri Marianna,
Ciuffreda Ludovica,
Mottolese Marcella,
Ribatti Domenico,
Vacca Angelo,
Del Rosso Mario,
Marcocci Lucia,
Zupi Gabriella,
Del Bufalo Donatella
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20413
Subject(s) - in vivo , matrigel , melanoma , biology , cancer research , in vitro , tumor progression , cell culture , metastasis , matrix metalloproteinase , phenotype , clone (java method) , cell growth , hypoxia (environmental) , angiogenesis , cancer , chemistry , gene , genetics , organic chemistry , oxygen
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.