Gharpure Kshipra M, Lara Olivia D, Wen Yunfei, Pradeep Sunila, LaFargue Chris, Ivan Cristina, Rupaimoole Rajesha, Hu Wei, Mangala Lingegowda S, Wu Sherry Y, Nagaraja Archana S, Baggerly Keith, Sood Anil K
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Oncotarget. 2018 May 18;9(38):25115-25126. doi: 10.18632/oncotarget.25344.
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.
原发性肿瘤细胞减灭术联合辅助化疗是卵巢癌的标准治疗方法。初次手术后的残留病灶与患者预后不良相关。此前，我们发现ADH1B是残留病灶的分子生物标志物。在本研究中，我们调查了ADH1B在促进卵巢癌细胞侵袭及导致残留病灶方面的功能作用。我们发现，ADH1B的过表达导致癌细胞表型更具浸润性，促进转移，增加癌细胞与间皮细胞的黏附，并增加细胞外基质降解。活细胞成像显示，与对照细胞相比，过表达ADH1B的癌细胞能有效清除间皮细胞层。此外，基因芯片分析显示，ADH1B影响与癌细胞迁移和侵袭相关的多个通路。我们还发现，缺氧会增加卵巢癌细胞中ADH1B的表达。总体而言，这些发现表明，ADH1B在促进卵巢癌细胞浸润的通路中起重要作用，并可能增加术后残留病灶的可能性。
