title: Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer.
abstract: 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.
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.|Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Vincent Center for Reproductive Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Foster
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.|Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Yang
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Jacson K
authors.initials: JK
authors.lastname: Shen
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Mankin
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Hornicek
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02114, USA.
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
authors.affiliation: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage; D012008:Recurrence; D015854:Up-Regulation / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D018960:Hyaluronan Receptors; D017239:Paclitaxel
keywords: CD44; Pgp; ovarian cancer; paclitaxel; tissue microarray
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