Abstract
Abstract Purpose: The clinical significance of Cluster of differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. Experimental Design: A unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Western blotting and Immunofluorescence assay determined the expression of CD44 and/or P-glycoprotein (Pgp) in ovarian cancer cell lines and the tumor tissues of a paclitaxel treated ovarian cancer xenograft mouse model. MTT assay, wound healing assay, and matrigel invasion assay were utilized to assess the proliferation, drug sensitivity, and migration/invasion ability, respectively. Results: Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Conclusions: Up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer. Citation Format: Yan Gao, Rosemary Foster, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan. Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 352. doi:10.1158/1538-7445.AM2015-352
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