title: Prosurvival function of the granulin-epithelin precursor is important in tumor progression and chemoresponse.
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.
authors.affiliation: Department of Experimental Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Gresin O
authors.initials: GO
authors.lastname: Pizarro
authors.forename: Xun Clare
authors.initials: XC
authors.lastname: Zhou
authors.forename: Anthony
authors.initials: A
authors.lastname: Koch
authors.forename: Mahmood
authors.initials: M
authors.lastname: Gharib
authors.forename: Sejal
authors.initials: S
authors.lastname: Raval
authors.forename: Keith
authors.initials: K
authors.lastname: Bible
authors.forename: Monica B
authors.initials: MB
authors.lastname: Jones
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D000077153:Progranulins
chemical_list: D000970:Antineoplastic Agents; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins