Prosurvival function of the granulin-epithelin precursor is important in tumor progression and chemoresponse

Gresin O. Pizarro, Clare Zhou Xun, Anthony Koch, Mahmood Gharib, Sejal Raval, Keith Bible, Monica B. Jones

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2339-2343
Number of pages5
JournalInternational Journal of Cancer
Volume120
Issue number11
DOIs
StatePublished - Jun 1 2007

Keywords

  • Chemoresistance
  • GEP/PCDGF
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Pizarro, G. O., Xun, C. Z., Koch, A., Gharib, M., Raval, S., Bible, K., & Jones, M. B. (2007). Prosurvival function of the granulin-epithelin precursor is important in tumor progression and chemoresponse. International Journal of Cancer, 120(11), 2339-2343. https://doi.org/10.1002/ijc.22559