CCL2 expression in primary ovarian carcinoma is correlated with chemotherapy response and survival outcomes

Amanda Nickles Fader, Nabila Rasool, Susan A.J. Vaziri, Toshiyuki Kozuki, Pieter W. Faber, Paul Elson, Charles V. Biscotti, Chad M. Michener, Peter G. Rose, Luis Rojas-Espaillat, Jerome L. Belinson, Mahrukh K. Ganapathi, Ram Ganapathi

Research output: Contribution to journalArticle

Abstract

CCL2, a chemokine, is expressed in normal human ovarian epithelium but down-regulated in ovarian adenocarcinomas. The association of CCL2 expression with chemotherapy response, invasion and survival outcomes was studied in patients with primary ovarian cancer (OC) and in ovarian cancer cell lines (OCCLs). Tumor specimens (>80% tumor) from patients with primary, advanced serous OC obtained at the time of cytoreductive surgery was used to isolate total RNA. The CCL2 gene expression evaluated by RT-PCR was investigated in relation to chemoresponselclinical outcomes in the OC patients and to sensitivity to cisplatin/paclitaxel in the OCCLs. In vitro invasion was measured by matrigel invasion and matrixmetallo-proteinase-9 (MMP-9) zymogram assays. Thirty-seven patients were included. In multivarible analyses that adjusted for the impact of debulking status, the CCL2 mRNA expression was correlated with objective complete response (p=0.01), chemosensitivity (p=0.04), and progression-free survival (PFS; p=0.006). These findings were corroborated in vitro in the OCCLs. The cells expressing higher levels of CCL2 were more sensitive to paclitaxel and cisplatin as compared to those lines expressing lower levels of this chemokine. Up-regulation of CCL2 in the PAT-7 cell line further enhanced the response of these cells to paclitaxel (p=0.0001) and led to decreased invasion (p=0.0009). Increased ovarian tumoral expression of CCL2 is associated with improved chemoresponse and survival outcomes, and higher levels of CCL2 in ovarian cancer cell lines are associated with increased chemosensitivity and decreased invasion in vitro.

Original languageEnglish (US)
Pages (from-to)4791-4798
Number of pages8
JournalAnticancer Research
Volume30
Issue number12
StatePublished - Dec 1 2010
Externally publishedYes

Keywords

  • CCL2
  • Chemosensitivity
  • Invasion
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Fader, A. N., Rasool, N., Vaziri, S. A. J., Kozuki, T., Faber, P. W., Elson, P., Biscotti, C. V., Michener, C. M., Rose, P. G., Rojas-Espaillat, L., Belinson, J. L., Ganapathi, M. K., & Ganapathi, R. (2010). CCL2 expression in primary ovarian carcinoma is correlated with chemotherapy response and survival outcomes. Anticancer Research, 30(12), 4791-4798.