Premium
Prosurvival function of the granulin‐epithelin precursor is important in tumor progression and chemoresponse
Author(s) -
Pizarro Gresin O.,
Zhou Xun Clare,
Koch Anthony,
Gharib Mahmood,
Raval Sejal,
Bible Keith,
Jones Monica B.
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22559
Subject(s) - ovarian cancer , cancer research , cisplatin , biology , tumor progression , in vivo , cell culture , phenotype , cancer , medicine , oncology , chemotherapy , gene , genetics
The granulin‐epithelin precursor (GEP/PCDGF), a 68–88 kDa secreted glycoprotein, has been shown to be an important growth and survival factor for ovarian cancer cells. Furthermore, GEP expression is a predictor of patient survival in metastatic ovarian cancer cells. Up to this point, however, the molecular mechanisms and clinical relevance of a GEP‐mediated prosurvival phenotype remain poorly characterized. We hypothesize that the prosurvival function of GEP is important in ovarian cancer tumor progression and chemoresponse. To explore this hypothesis, we examined the effects of GEP overexpression on migration, invasion and cisplatin (CDDP) chemosensitivity in the ovarian cancer cell line A2780. Full length GEP transfectants demonstrated an increased capacity to migrate and invade their substratum when compared to empty vector controls. In addition, GEP overexpression was associated with CDDP chemoresistance. Finally, GEP overexpression increased tumor formation and protected cells from tumor regression in response to CDDP treatment in vivo . Taken together, these data support a role for GEP in tumor progression and development of drug resistance. © 2006 Wiley‐Liss, Inc.