Li Liu1,2, Bo Yin3, Zhu Yi4, XiuJuan Liu5, ZhiQian Hu6, WenChao Gao6, HaiWen Yu7, QingQuan Li8. 1. Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. 3. Department of Radiology, HuaShan Hospital, Fudan University, Shanghai, China. 4. Department of Radiation Oncology, Eye and Ent Hospital, Fudan University, Shanghai, China. 5. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. 6. Department of General Surgery, ChangZheng Hospital, Second Military Medical University, Shanghai, China. 7. Department of Surgery, Jiading Nanxiang Hospital, Shanghai, 201802, China. yuhaiww@163.com. 8. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. 061101040@fudan.edu.cn.
Abstract
BACKGROUND: Cancer stem cells (CSCs) are believed to form metastases. We sought to determine whether CD70 + subpopulation in human breast cancers represents the CSCs accounting for distant metastasis. METHODS: We measured the expression levels of CD70 in breast cancer cell lines and 122 primary breast cancer samples. We characterized the functional roles of CD70 + subpopulation in distant metastasis of breast cancers. RESULTS: We observed a distinct pattern of CD70 expression in a panel of primary breast carcinoma samples, indicating that CD70 serves as a biomarker of lung-specific metastasis. CD70- and CD70+ cell populations isolated from breast cancer cell lines exhibited epithelial and mesenchymal phenotypes, respectively. CD70+ cells, but not CD70- cells, possessed self-renewal and differentiation potentials. Tumorsphere formation in suspension cultures and in vivo tumorigenicity were significantly greater in CD70+ cells than in CD70- cells. Furthermore, the development of lung metastases induced by orthotopic injection was markedly increased in mice inoculated with CD70 + cells. CD70 contributed to the promotion of lung metastases by enhancing self-renewal potential of CD70 + cells. CONCLUSIONS: We isolated CSCs from primary human breast cancers and found that CD70 + subpopulations mediate lung-specific metastasis. These findings might be used to aid in selection of patients for postoperative adjuvant therapy.
BACKGROUND: Cancer stem cells (CSCs) are believed to form metastases. We sought to determine whether CD70 + subpopulation in humanbreast cancers represents the CSCs accounting for distant metastasis. METHODS: We measured the expression levels of CD70 in breast cancer cell lines and 122 primary breast cancer samples. We characterized the functional roles of CD70 + subpopulation in distant metastasis of breast cancers. RESULTS: We observed a distinct pattern of CD70 expression in a panel of primary breast carcinoma samples, indicating that CD70 serves as a biomarker of lung-specific metastasis. CD70- and CD70+ cell populations isolated from breast cancer cell lines exhibited epithelial and mesenchymal phenotypes, respectively. CD70+ cells, but not CD70- cells, possessed self-renewal and differentiation potentials. Tumorsphere formation in suspension cultures and in vivo tumorigenicity were significantly greater in CD70+ cells than in CD70- cells. Furthermore, the development of lung metastases induced by orthotopic injection was markedly increased in mice inoculated with CD70 + cells. CD70 contributed to the promotion of lung metastases by enhancing self-renewal potential of CD70 + cells. CONCLUSIONS: We isolated CSCs from primary humanbreast cancers and found that CD70 + subpopulations mediate lung-specific metastasis. These findings might be used to aid in selection of patients for postoperative adjuvant therapy.
Entities:
Keywords:
Breast carcinoma; CD70; Cancer stem cells; Lung metastasis; Self-renewal
Authors: Tal Flieswasser; Astrid Van den Eynde; Jonas Van Audenaerde; Jorrit De Waele; Filip Lardon; Carsten Riether; Hans de Haard; Evelien Smits; Patrick Pauwels; Julie Jacobs Journal: J Exp Clin Cancer Res Date: 2022-01-06
Authors: Ting-Ting Shan; Xuan Zhao; Zhen Zhang; Jing-Pu Wang; Yi Zhang; Yang Yang; Song Zhao Journal: Cancer Manag Res Date: 2020-08-05 Impact factor: 3.989