Recombinant soluble CD226 protein directly inhibits cancer cell proliferation in vitro.
Interactions between CD155 and nectins on tumor cells have been reported to potentially inhibit tumor growth. CD226, a receptor that recognizes CD155 and CD112, is an activation receptor of NK and T cells by which immune cells may attack a tumor. The purpose of this study is to explore whether soluble CD226 (sCD226) directly inhibits tumor growth by binding CD155 or CD112 on tumor cells. We expressed, purified and confirmed the identity of recombinant sCD226 (19aa-248aa) and then examined the effect of sCD226 on tumor cell growth using CD226 ligand (CD155 and CD112)-expressing cancer cell lines (K562, HeLa). After 3days of co-culture with sCD226, we found that the numbers of K562 and HeLa cells were significantly reduced but those of a CD226-blocking mAb specifically attenuated the inhibitory effects of sCD226. We also noted that the sCD226 protein could compete with a PE-conjugated anti-CD112 antibody in flow cytometric analysis and block the binding of the PE-conjugated anti-CD112 antibody to tumor cells. Mechanistic studies using flow cytometric analysis demonstrated that sCD226 inhibited the division of CFSE (carboxyfluorescein diacetate succinimidyl ester)-labeled K562 cells by delaying the cell cycle. In addition, we observed that sCD226 might have an impact on the metastatic potential of solid tumors in vitro. These results demonstrated that sCD226 molecule might be a potential biotherapy against tumor for further development.
Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Shengke
S
Hou
Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Xiaodong
X
Zheng
Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
Haiming
H
Wei
Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China.
Zhigang
Z
Tian
Department of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, China. Electronic address: sunr@ustc.edu.cn.
Rui
R
Sun
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003412:Cricetulus; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D009369:Neoplasms; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000494:pharmacology; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000970:Antineoplastic Agents; D000098862:T Lineage-Specific Activation Antigen 1; D011994:Recombinant Proteins
Cell proliferation; Soluble CD226; Tumor