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 Selanere Mangala, Sherry Wu, Archana S. Nagaraja, Keith A Baggerly, Anil K Sood

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Pages25115-25126
Number of pages12
JournalOncotarget
Volume9
Issue number38
DOIs
StatePublished - May 18 2018

Fingerprint

Ovarian Neoplasms
Neoplasms
Adjuvant Chemotherapy
Cell Adhesion
Extracellular Matrix
Biomarkers
Neoplasm Metastasis
Phenotype

Keywords

  • Alcohol dehydrogenase
  • ECM degradation
  • Mesothelial clearance
  • Residual disease

ASJC Scopus subject areas

  • Oncology

Cite this

ADH1B promotes mesothelial clearance and ovarian cancer infiltration. / Gharpure, Kshipra M.; Lara, Olivia D.; Wen, Yunfei; Pradeep, Sunila; LaFargue, Chris; Ivan, Cristina; Rupaimoole, Rajesha; Hu, Wei; Mangala, Lingegowda Selanere; Wu, Sherry; Nagaraja, Archana S.; Baggerly, Keith A; Sood, Anil K.

In: Oncotarget, Vol. 9, No. 38, 18.05.2018, p. 25115-25126.

Research output: Contribution to journalArticle

Gharpure, KM, Lara, OD, Wen, Y, Pradeep, S, LaFargue, C, Ivan, C, Rupaimoole, R, Hu, W, Mangala, LS, Wu, S, Nagaraja, AS, Baggerly, KA & Sood, AK 2018, 'ADH1B promotes mesothelial clearance and ovarian cancer infiltration' Oncotarget, vol. 9, no. 38, pp. 25115-25126. https://doi.org/10.18632/oncotarget.25344
Gharpure, Kshipra M. ; Lara, Olivia D. ; Wen, Yunfei ; Pradeep, Sunila ; LaFargue, Chris ; Ivan, Cristina ; Rupaimoole, Rajesha ; Hu, Wei ; Mangala, Lingegowda Selanere ; Wu, Sherry ; Nagaraja, Archana S. ; Baggerly, Keith A ; Sood, Anil K. / ADH1B promotes mesothelial clearance and ovarian cancer infiltration. In: Oncotarget. 2018 ; Vol. 9, No. 38. pp. 25115-25126.
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