Work

ADH1B promotes mesothelial clearance and ovarian cancer infiltration

Year: 2018

Type: article

Abstract: // Kshipra M. Gharpure 1, * , Olivia D. Lara 1, * , Yunfei Wen 1 , Sunila Pradeep 1 , Chris LaFargue 1 , Cristina Ivan 2, 3 , Rajesha Rupaimoole 4 , Wei Hu 1 , Lingegowda S. Mangala 1, 3 , Sherry Y. Wu 1 , Archana S. Nagaraja 1 , Keith Baggerly 5 and Anil K. Sood 1, 3, 6, * 1 Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 2 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 3 Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 4 Department of Pathology, Institute of RNA Medicine, Beth Israel Deaconess Medical Center Cancer Center, Harvard Medical School, Boston, MA 02215, USA 5 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 6 Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA * These authors contributed equally to this work Correspondence to: Anil K. Sood, email: [email protected] Keywords: alcohol dehydrogenase; residual disease; mesothelial clearance; ECM degradation Received: January 31, 2018 Accepted: April 21, 2018 Published: May 18, 2018 ABSTRACT Primary debulking surgery followed by adjuvant chemotherapy is the standard treatment for ovarian cancer. Residual disease after primary surgery is associated with poor patient outcome. Previously, we discovered ADH1B to be a molecular biomarker of residual disease. In the current study, we investigated the functional role of ADH1B in promoting ovarian cancer cell invasiveness and contributing to residual disease. We discovered that ADH1B overexpression leads to a more infiltrative cancer cell phenotype, promotes metastasis, increases the adhesion of cancer cells to mesothelial cells, and increases extracellular matrix degradation. Live cell imaging revealed that ADH1B-overexpressing cancer cells efficiently cleared the mesothelial cell layer compared to control cells. Moreover, gene array analysis revealed that ADH1B affects several pathways related to the migration and invasion of cancer cells. We also discovered that hypoxia increases ADH1B expression in ovarian cancer cells. Collectively, these findings indicate that ADH1B plays an important role in the pathways that promote ovarian cancer cell infiltration and may increase the likelihood of residual disease following surgery.

Source: Oncotarget

DOI: 10.18632/oncotarget.25344