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Potential function of CTLA-4 in the tumourigenic capacity of melanoma stem cells.
Zhang, Bingyu; Dang, Jianzhong; Ba, Diandian; Wang, Cencen; Han, Juan; Zheng, Fang.
Afiliação
  • Zhang B; Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
  • Dang J; Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
  • Ba D; Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
  • Wang C; Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
  • Han J; Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
  • Zheng F; Department of Paediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Oncol Lett ; 16(5): 6163-6170, 2018 Nov.
Article em En | MEDLINE | ID: mdl-30344757
Extensive clinical evidence supports that cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed in a variety of human malignant tumour cells in addition to T cells. In certain types of cancer, the overexpression of CTLA-4 is associated with poor patient prognosis. However, few studies have demonstrated the effects of tumour-intrinsic CTLA-4 in cancer stem cells, including melanoma stem cells (MSCs). In the present study, it was demonstrated that melanoma cell-intrinsic CTLA-4 induced tumour cell proliferation in vitro and suppressed tumour cell apoptosis. Furthermore, CTLA-4 was expressed in aldehyde dehydrogenase (ALDH)+ MSCs. CTLA-4 inhibited MSCs proliferation in vitro by blocking antibodies and significantly downregulated ALDH1A1, ALDH1A3 and ALDH2 mRNA expression (P<0.01). Functionally, blocking CTLA-4 in melanoma cell lines suppressed the properties of stem-like cells, including ALDH activity and significantly suppressed the ability of these cells to form spheres in vitro (P<0.05). In addition, the blocking of CTLA-4 in melanoma cells suppressed the properties of stem-like cells in vivo, including the capacity for tumourigenesis. The presence of residual ALDH+ MSCs within the tumour was observed, and the blocking CTLA-4 significantly decreased the number of residual ALDH+ MSCs in vivo (P<0.01). Altogether, these results indicate the identification of a novel mechanism underlying melanoma progression in the present study and that CTLA-4-targeted therapy may benefit candidate CTLA-4-targeted therapy by improving the long-term outcome for patients with advanced stages of melanoma.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Oncol Lett Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Oncol Lett Ano de publicação: 2018 Tipo de documento: Article