Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer
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Yan Gao1,2, Rosemary Foster3, Xiaoqian Yang1,2, Yong Feng1, Jacson K. Shen1, Henry J. Mankin1, Francis J. Hornicek1, Mansoor M. Amiji4, Zhenfeng Duan1
1Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
2Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
3Vincent Center for Reproductive Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
4Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02114, USA
Zhenfeng Duan, e-mail: [email protected]
Keywords: ovarian cancer, CD44, tissue microarray, Pgp, paclitaxel
Received: November 22, 2014 Accepted: January 26, 2015 Published: March 13, 2015
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. In this study, 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. 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. Thus, 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.
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