Oncotarget

Research Papers:

ADH1B promotes mesothelial clearance and ovarian cancer infiltration

Kshipra M. Gharpure, Olivia D. Lara, Yunfei Wen, Sunila Pradeep, Chris LaFargue, Cristina Ivan, Rajesha Rupaimoole, Wei Hu, Lingegowda S. Mangala, Sherry Y. Wu, Archana S. Nagaraja, Keith Baggerly and Anil K. Sood _

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Oncotarget. 2018; 9:25115-25126. https://doi.org/10.18632/oncotarget.25344

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Abstract

Kshipra M. Gharpure1,*, Olivia D. Lara1,*, Yunfei Wen1, Sunila Pradeep1, Chris LaFargue1, Cristina Ivan2,3, Rajesha Rupaimoole4, Wei Hu1, Lingegowda S. Mangala1,3, Sherry Y. Wu1, Archana S. Nagaraja1, Keith Baggerly5 and Anil K. Sood1,3,6,*

1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

2Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

3Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

4Department of Pathology, Institute of RNA Medicine, Beth Israel Deaconess Medical Center Cancer Center, Harvard Medical School, Boston, MA 02215, USA

5Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

6Department 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: asood@mdanderson.org

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.


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