| Title | Cancer stem cell property and gene signature in bone-metastatic Breast Cancer cells |
| Authors | Luo, An Xu, Yue Li, Shujun Bao, Jinxia Lu, Jinhui Ding, Nan Zhao, Qian Fu, Yuting Liu, Fei Cho, William C. Wei, Xunbin Wang, Haiyun Yu, Zuoren |
| Affiliation | Tongji Univ, Shanghai East Hosp, Res Ctr Translat Med, Sch Life Sci & Technol, Shanghai 200120, Peoples R China Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai, Peoples R China Tongji Univ, Shanghai East Hosp, Dept Gastroenterol, Shanghai 200120, Peoples R China Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai, Peoples R China Peking Univ, Biomed Engn Dept, Beijing, Peoples R China Third Hosp BaoGang Grp, Baotou, Peoples R China Queen Elizabeth Hosp, Dept Clin Oncol, Kowloon, Hong Kong, Peoples R China |
| Keywords | LUNG |
| Issue Date | 2020 |
| Publisher | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES |
| Abstract | The majority of the deaths from breast cancer is due to metastasis. Bone is the most common organ to which breast cancer cells metastasize. The mechanism regulating the bone-metastatic preference remains unclear; there is a lack of a gene signature to distinguish bone-metastatic breast cancer cells. Herein, florescence-labeled MDA-MB-231 cells were transplanted into the fat pads of of the mammary gland in nude mice to generate breast tumors. Tumor cells invaded into the circulation were tracked by in vivo flow cytometry system. Metastatic tumor cells in the bone were isolated using fluorescent-activated cell sorting technique, followed by assays of cell colony formation, migration and invasion, mammosphere formation in vitro, mammary gland tumorigenesis in vivo, and Next-Generation Sequencing analysis as well. Through tumor regeneration and cell sorting, two bone-metastatic cell sublines were derived from MDA-MB-231 cells; which showed higher abilities to proliferate, migrate, invade and epithelial-to-mesenchymal transit in vitro, and stronger ability to regenerate tumors and metastasize to the bone in vivo. Both cell sublines exhibited cancer stem cell-like characteristics including higher expression levels of stem cell markers and stronger ability for mommaspheres formation. Furthermore, a Normal Distribution-like pattern of the bone-metastatic cells invading into circulation was firstly identified. Deep-sequencing analysis indicated upregulation of multiple signaling pathways in regulating EMT, cell membrane budding and morphologic change, lipid metabolism, and protein translation, which are required to provide adequate metabolic enzymes, structural proteins, and energy for the cells undergoing metastasis. In conclusion, we established two bone-metastatic breast cancer cell sublines, carrying higher degree of stemness and malignancy. The gene signature distinguishing the bone-metastatic breast cancer cells holds therapeutic potentials in prevention of breast cancer metastasis to the bone. |
| URI | http://hdl.handle.net/20.500.11897/590771 |
| ISSN | 1449-2288 |
| DOI | 10.7150/ijbs.45693 |
| Indexed | SCI(E) |
| Appears in Collections: | 待认领 |
