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Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer.

Abstract

Macrophage-targeted therapy offers new options for intractable pancreatic ductal adenocarcinoma (PDAC), which has a low 5-year survival rate. However, the factors regulating the biological function and phenotype of macrophages in PDAC are incompletely understood. Here, we found that CD51 was positively associated with the poor prognosis of PDAC patients and was highly expressed on macrophages but not on pancreatic cancer cells. Subsequently, we found that CD51 was a marker of macrophages, which promoted the stemness of pancreatic cancer cells. Furthermore, knockdown of CD51 in macrophages drove macrophages toward an M1-like phenotype. Mechanistically, macrophage-expressed CD51 contributed to the acquisition of stemness traits of pancreatic cancer cells by regulating the TGF-β1/smad2/3 pathway. Our data demonstrate the central role played by macrophage-expressed CD51 in the acquisition of stemness traits of pancreatic cancer cells through the paracrine induction of TGF-β1. We first show the connection between the CD51/TGF-β1/smad2/3 axis and PDAC cancer stem cell properties and then indicate that CD51-targeted therapy is a new therapeutic modality for PDAC.

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  • Authors+Show Affiliations

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou,Guangdong Province,510655, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, 510655, China.

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    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

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    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

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    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Urology, State Key Laboratory of Oncology in South China, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong Province, 510120, China.

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

    ,

    Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, 510080, China.

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China.

    ,

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China. Electronic address: zhihuali_sysu@163.com.

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China; Department of Pancreatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510120, China. Electronic address: Chenrufu@mail.sysu.edu.com.

    Source

    Cancer letters 459: 2019 Sep 10 pg 204-215

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31199988

    Citation

    Zhang, Bin, et al. "Macrophage-expressed CD51 Promotes Cancer Stem Cell Properties Via the TGF-β1/smad2/3 Axis in Pancreatic Cancer." Cancer Letters, vol. 459, 2019, pp. 204-215.
    Zhang B, Ye H, Ren X, et al. Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer. Cancer Lett. 2019;459:204-215.
    Zhang, B., Ye, H., Ren, X., Zheng, S., Zhou, Q., Chen, C., ... Chen, R. (2019). Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer. Cancer Letters, 459, pp. 204-215. doi:10.1016/j.canlet.2019.06.005.
    Zhang B, et al. Macrophage-expressed CD51 Promotes Cancer Stem Cell Properties Via the TGF-β1/smad2/3 Axis in Pancreatic Cancer. Cancer Lett. 2019 Sep 10;459:204-215. PubMed PMID: 31199988.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer. AU - Zhang,Bin, AU - Ye,Huilin, AU - Ren,Xiaofan, AU - Zheng,Shangyou, AU - Zhou,Quanbo, AU - Chen,Changhao, AU - Lin,Qing, AU - Li,Guolin, AU - Wei,Lusheng, AU - Fu,Zhiqiang, AU - Zhang,Yuting, AU - Hu,Chonghui, AU - Li,Zhihua, AU - Chen,Rufu, Y1 - 2019/06/12/ PY - 2019/01/10/received PY - 2019/06/01/revised PY - 2019/06/10/accepted PY - 2019/6/15/pubmed PY - 2019/6/15/medline PY - 2019/6/15/entrez KW - Biomarker KW - Cancer stem cell KW - Integrin KW - Pancreatic ductal adenocarcinoma KW - Tumor-associated macrophage SP - 204 EP - 215 JF - Cancer letters JO - Cancer Lett. VL - 459 N2 - Macrophage-targeted therapy offers new options for intractable pancreatic ductal adenocarcinoma (PDAC), which has a low 5-year survival rate. However, the factors regulating the biological function and phenotype of macrophages in PDAC are incompletely understood. Here, we found that CD51 was positively associated with the poor prognosis of PDAC patients and was highly expressed on macrophages but not on pancreatic cancer cells. Subsequently, we found that CD51 was a marker of macrophages, which promoted the stemness of pancreatic cancer cells. Furthermore, knockdown of CD51 in macrophages drove macrophages toward an M1-like phenotype. Mechanistically, macrophage-expressed CD51 contributed to the acquisition of stemness traits of pancreatic cancer cells by regulating the TGF-β1/smad2/3 pathway. Our data demonstrate the central role played by macrophage-expressed CD51 in the acquisition of stemness traits of pancreatic cancer cells through the paracrine induction of TGF-β1. We first show the connection between the CD51/TGF-β1/smad2/3 axis and PDAC cancer stem cell properties and then indicate that CD51-targeted therapy is a new therapeutic modality for PDAC. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/31199988/Macrophage-expressed_CD51_promotes_cancer_stem_cell_properties_via_the_TGF-β1/smad2/3_axis_in_pancreatic_cancer L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(19)30366-0 DB - PRIME DP - Unbound Medicine ER -