Expression of Osteoblast-Specific Factor 2 (OSF-2, Periostin) Is Associated with Drug Resistance in Ovarian Cancer Cell Lines.

Karolina Sterzyńska,Radosław Januchowski,Marta Nowacka,Jacek Brązert,Dominika Kaźmierczak,Andrzej Klejewski,Michał Nowicki,Monika Świerczewska,Karolina Wojtowicz

doi:10.3390/ijms20163927

Abstract

One of the main obstacles to the effective treatment of ovarian cancer patients continues to be the drug resistance of cancer cells. Osteoblast-Specific Factor 2 (OSF-2, Periostin) is a secreted extracellular matrix protein (ECM) expressed in fibroblasts during bone and teeth development. Expression of OSF-2 has been also related to the progression and drug resistance of different tumors. The present study investigated the role of OSF-2 by evaluating its expression in the primary serous ovarian cancer cell line, sensitive (W1) and resistant to doxorubicin (DOX) (W1DR) and methotrexate (MTX) (W1MR). The OSF-2 transcript (real-time PCR analysis), protein expression in cell lysates and cell culture medium (western blot), and expression of the OSF-2 protein in cell lines (immunofluorescence) were investigated in this study. Increased expression of OSF-2 mRNA was observed in drug-resistant cells and followed by increased protein expression in cell culture media of drug-resistant cell lines. A subpopulation of ALDH1A1-positive cells was noted for W1DR and W1MR cell lines; however, no direct co-expression with OSF-2 was demonstrated. Both drugs induced OSF-2 expression after a short period of exposure of the drug-sensitive cell line to DOX and MTX. The obtained results indicate that OSF-2 expression might be associated with the development of DOX and MTX resistance in the primary serous W1 ovarian cancer cell line.

Highlights

Chemoresistance of cancer cells—inherent or developed during treatment—remains an obstacle to the effective treatment of ovarian cancer patients [1]
Since we previously described the subpopulations of aldehyde dehydrogenase isoform 1A1 (ALDH1A1)-positive cells in PAC- and TOP-resistant ovarian cancer cell lines derived from W1 and A2780 cell lines [13,42], we wanted to specify whether such dependence could be observed for W1DR and W1MR cell lines
Rabbit polyclonal anti-Osteoblast-Specific factor 2 (OSF-2) Ab was obtained from Proteintech (Manchester, UK), rabbit monoclonal anti-ALDH1A1 Ab was purchased from Abcam (Cambridge, UK), mouse monoclonal anti-ALDH1A1 Ab was purchased from ABGENT (San Diego, CA, USA), and rabbit polyclonal anti-glyceraldehyde-3-phosphate dehydrogenase (GADPH) Ab was purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA)

Summary

Introduction

Chemoresistance of cancer cells—inherent or developed during treatment—remains an obstacle to the effective treatment of ovarian cancer patients [1]. ECM components—both structural, like laminins and collagens, or soluble, like growth factors and matricellular proteins—can interact with cancer cell surface receptors (mainly integrins) and activate different drug resistance mechanisms [3,4]. This kind of resistance, known as cell-adhesion-mediated drug resistance (CAM-DR) is observed both in vivo [7] and in vitro [8], as it was observed in drug-resistant cancer cell lines of breast [9] and ovarian origin [10,11,12,13]

Methods

Results

Conclusion