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Ying Peng, 1 Xiang-Xiang Zhan, 2 Yi Cao, 3 Han-Wen Zhang, 1 Wei-Han Cao, 1, 2 Yan-Jun Su, 1, 2 Chang Diao, 2 Qiang-Ming Sun, 1, 2, 4, 5 Ruo-Chuan Cheng 1, 2, 4, 5 1Kunming Medical University of Yunnan Province, Kunming, Yunnan 650500, People’s Republic of China; 2Thyroid Disease Diagnosis and Treatment Center, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, People’s Republic of China; 3Longyan Jianhai Medical and Pharmaceutical Technology Co., Ltd., Longyan, Fujian 364000, People’s Republic of China; 4Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, People’s Republic of China; 5Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Diseases, Kunming 650118, People’s Republic of ChinaCorrespondence: Ruo-Chuan Cheng; Qiang-Ming Sun Email cruochuan@foxmail.com; qsun@imbcams.com.cnBackground: Thomsen–Friedenreich antibody (TF-Ab) is a specific antibody against the Thomsen–Friedenreich antigen (TF-Ag). At present, studies on a number of other tumors have shown that TF-Ab can effectively inhibit metastasis and induce apoptosis in tumor cells. However, the role of TF-Ab in thyroid cancer (TC) remains unclear.Materials and Methods: Normal subjects and patients with primary papillary TC with or without lymph node metastasis were tested for TF-Ab expression by enzyme-linked immunosorbent assays (ELISAs). Immunofluorescence was used to assess the expression of TF-Ag in thyroid papillary carcinoma with or without lymph node metastasis and undifferentiated cancer tissues. To evaluate the role of TF-Ab in TC, the effects of TF monoclonal antibody (mAb A78-G/A7) on cell biological function were investigated by MTT assays, flow cytometry, adhesion assays and transwell experiments.Results: Compared with normal individuals, TF-Ab levels in patients with TC were decreased, but no changes were observed with respect to lymph node metastasis. The expression of TF-Ag in TC tissues was relatively higher than that detected in adjacent tissues, but it was not affected by the presence or absence of lymph node metastasis. Upon treatment mAb A78-G/A7 treating, TC cell cycles were affected, meanwhile the abilities to adhere, invade and migrate were also significantly reduced.Conclusion: The results of the present study showed that mAb A78-G/A7 could affect the invasion and migration of all assayed TC cell lines. The effects of mAb A78-G/A7 on the cell cycle, adhesion, invasion and migration of TC cells were more significant than those observed for proliferation and apoptosis.Keywords: Thomsen–Friedenreich antibody, TF-Ab, Thomsen–Friedenreich antigen, TF-Ag, mAb A78-G/A7, thyroid cancer, TC

Hongchao Jiang,1,2 Ceshi Chen,3 Qiangming Sun,4 Jing Wu,3 Lijuan Qiu,4 Change Gao,5 Weiqing Liu,5 Jun Yang,5 Nie Jun,2 Jian Dong2 1Department of Oncology, The Affiliated Children’s Hospital of Kunming Medical University, 2Department of Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Provincial Tumor Hospital, 3Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 4Molecular Epidemiology Joint Laboratory, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, 5Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republicof China Background: Semaphorin 4D (Sema4D) is highly expressed in certain types of tumors and functions in the regulation of tumor angiogenesis and growth. However, it is still not clear regarding the roles of Sema4D in breast cancer. This study was designed to explore the effects of Sema4D on proliferation, cell cycle progression, apoptosis, invasion, migration, tumor growth, and angiogenesis in breast cancer.Materials and methods: The expression level of Sema4D was investigated in MCF10A, 184A1, HCC1937, MDA-MB-468, MDA-MB-231, Hs578T, BT474, MCF-7, and T47D breast cancer cell lines by Western blotting analysis. Sema4D downregulation or overexpression was established by infection with lentiviruses-encoding Sema4D short hairpin RNA (shRNA) or Sema4D. To evaluate the effects of Sema4D on cell proliferation, cell cycle progression, apoptosis, invasion, and migration of MDA-MB-231 and MDA-MB-468 cells, methods including MTT assay, flow cytometry, wound healing assay, and transwell experiments were applied. BALB/c nude mice were injected with MDA-MB-231 cells, which were respectively infected with lentiviruses-encoding Sema4D, Sema4D shRNA, and GFP, followed by tumor angiogenesis assay.Results: Sema4D was expressed at higher levels in breast cancer cell lines compared with the normal human breast epithelial cell lines, especially in MDA-MB-231 and MDA-MB-468 cells. Cell proliferation ability was remarkably inhibited in Sema4D downregulated condition, whereas the proportions of cells in the G0/G1 phase and apoptosis increased in MDA-MB-231 and MDA-MB-468 cells. In addition, the invasion and migration abilities of these cells were obviously reduced. Xenograft growth as well as angiogenesis was inhibited when infected with lentiviruses-encoding Sema4D shRNA in vivo.Conclusion: Downregulation of Sema4D had notable influence on cell proliferation ability, invasion, migration, and apoptosis of both MDA-MB-231 and MDA-MB-468 cells. Furthermore, infection with lentiviruses-encoding Sema4D shRNA obviously inhibited tumor growth and angiogenesis in BALB/c nude mice. Our results showed that Sema4D may represent a novel therapeutic target for human breast cancer. Keywords: semaphorin 4D, breast cancer, apoptosis, angiogenesis, proliferation