The Role of Matrix Gla Protein (MGP) Expression in Paclitaxel and Topotecan Resistant Ovarian Cancer Cell Lines

• Published in: International journal of molecular sciences 2018-09, Vol.19 (10), p.2901
• Main Authors: Sterzyńska, Karolina, Klejewski, Andrzej, Wojtowicz, Karolina, Świerczewska, Monika, Andrzejewska, Małgorzata, Rusek, Damian, Sobkowski, Maciej, Kędzia, Witold, Brązert, Jacek, Nowicki, Michał, Januchowski, Radosław
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Calcium-Binding Proteins - analysis; Calcium-Binding Proteins - genetics; Cell Line, Tumor; Drug Resistance, Neoplasm; Extracellular Matrix Proteins - analysis; Extracellular Matrix Proteins - genetics; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Matrix Gla Protein; ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Paclitaxel - pharmacology; paclitaxel resistance; Topoisomerase I Inhibitors - pharmacology; Topotecan - pharmacology; topotecan resistance
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms19102901

The major cause of ovarian cancer treatment failure in cancer patients is inherent or acquired during treatment drug resistance of cancer. Matrix Gla protein (MGP) is a secreted, non-collagenous extracellular matrix protein involved in inhibition of tissue calcification. Recently, MGP expression was related to cellular differentiation and tumor progression. A detailed MGP expression analysis in sensitive (A2780) and resistant to paclitaxel (PAC) (A2780PR) and topotecan (TOP) (A2780TR) ovarian cancer cell lines and their corresponding media was performed. mRNA level (real time PCR analysis) and protein expression in cell lysates and cell culture medium (Western blot analysis) and protein expression in cancer cells (immunofluorescence analysis) and cancer patient lesions (immunohistochemistry) were determined in this study. We observed increased expression of MGP in PAC and TOP resistant cell lines at both mRNA and protein level. MGP protein was also detected in the corresponding culture media. Finally, we detected expression of MGP protein in ovarian cancer lesions from different histological type of cancer. MGP is an important factor that might contribute to cancer resistance mechanism by augmenting the interaction of cells with ECM components leading to increased resistance of ovarian cancer cells to paclitaxel and topotecan. Expression found in ovarian cancer tissue suggests its possible role in ovarian cancer pathogenesis.