EM2D9, A monoclonal antibody against integrin α5β1, has potent antitumor activity on endometrial cancer in vitro and in vivo

Yinyan Xu; Yi Li; Jiahui Pan; Xing Kang; Xu Zhang; Xinyi Feng; Shucheng Li; Chengxi Li; Jinku Zhang; Chong Li; Guoqing Wang

doi:10.1016/j.canlet.2020.02.019

EM2D9, A monoclonal antibody against integrin α5β1, has potent antitumor activity on endometrial cancer in vitro and in vivo

Cancer Lett. 2020 Jul 28:483:66-74. doi: 10.1016/j.canlet.2020.02.019. Epub 2020 Mar 3.

Authors

Yinyan Xu¹, Yi Li², Jiahui Pan¹, Xing Kang³, Xu Zhang³, Xinyi Feng⁴, Shucheng Li⁵, Chengxi Li⁵, Jinku Zhang⁶, Chong Li⁷, Guoqing Wang⁸

Affiliations

¹ The Key Laboratory for Bionics Engineering, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun, 130021, China.
² Department of Anesthesiology, Peking University Third Hospital, Beijing, 100083, China.
³ Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
⁴ Beijing No.4 High School International Campus, Beijing, 100031, China.
⁵ Beijing Jianlan Institute of Medicine, Beijing, 100190, China.
⁶ Baoding First Central Hospital, Baoding, Hebei, 071000, China.
⁷ Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; Beijing Jianlan Institute of Medicine, Beijing, 100190, China. Electronic address: lichong@moon.ibp.ac.cn.
⁸ The Key Laboratory for Bionics Engineering, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun, 130021, China. Electronic address: qing@jlu.edu.cn.

PMID: 32142917
DOI: 10.1016/j.canlet.2020.02.019

Abstract

Endometrial cancer, a type of primary epithelial malignant tumor in the endometrium, is one of the three most common malignant tumors of the female reproductive system. While the incidence of endometrial cancer has been recently rising, its etiology remains unclear. In this study we found that EM2D9, an independently developed monoclonal antibody, specifically recognized endometrial cancer cells; we further determined that EM2D9 target protein was α5β1. In vitro and in vivo experiments showed that EM2D9 inhibited the migration of endometrial cancer cells. Real-time quantitative PCR results showed that the expression of CD151 mRNA in endometrial carcinoma cells significantly decreased after EM2D9 treatment. We also found that EM2D9 affected the FAK signaling pathway. Collectively, these results shed light on a new mechanism for the development of endometrial carcinoma.

Keywords: CD151; Cell migration; EM2D9; Endometrial carcinoma; α5β1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / pharmacology*
Antineoplastic Agents, Immunological / pharmacology*
Cell Line, Tumor
Cell Movement / drug effects*
Endometrial Neoplasms / drug therapy*
Endometrial Neoplasms / genetics
Endometrial Neoplasms / metabolism
Endometrial Neoplasms / pathology
Female
Focal Adhesion Kinase 1 / metabolism
Humans
Integrin alpha5beta1 / antagonists & inhibitors*
Integrin alpha5beta1 / metabolism
Integrin beta1* / metabolism
Integrins / antagonists & inhibitors*
Integrins / metabolism
Mice, Inbred NOD
Mice, SCID
Signal Transduction
Tetraspanin 24 / genetics
Tetraspanin 24 / metabolism
Xenograft Model Antitumor Assays

Substances

Antibodies, Monoclonal
Antineoplastic Agents, Immunological
CD151 protein, human
ITGA5 protein, human
Integrin alpha5beta1
Integrin beta1
Integrins
Itgb1 protein, human
Tetraspanin 24
Focal Adhesion Kinase 1
PTK2 protein, human