title: Hypoxia regulates stemness of breast cancer MDA-MB-231 cells.
abstract: Human breast cancers include cancer stem cell populations as well as non-tumorigenic cancer cells. Breast cancer stem cells possess self-renewal capability and thus are the root cause of recurrence and metastasis of malignant tumors. Hypoxia is a fundamental pathological feature of solid tumor tissues and exerts a wide range of effects on the biological behavior of cancer cells. However, there is little information on the role of hypoxia in modulating the stemness of breast cancer cells. In the present study, we cultured MDA-MB-231 cells in a hypoxic gas mixture to simulate the hypoxic environment in tissues and to determine how hypoxia conditions could affect the cell proliferation, apoptosis, cytotoxicity, and colony-forming ability. Expression of the stem cell phenotype CD24(-)CD44(+)ESA(+) was analyzed to assess the effects of hypoxia on stemness transformation in MDA-MB-231 cells. Our results found that the cell toxicity of MDA-MB-231 cells was not affected by hypoxia. Hypoxia could slightly inhibit the growth of MDA-MB-231 cells, but the inhibitory effect is not significant when compared with normoxic control. Moreover, hypoxia significantly blocked the apoptosis in MDA-MB-231 cells (P < 0.05). The proportion of CD24(-)CD44(+)ESA(+) cells in MDA-MB-231 cells was increased greatly after they were treated with hypoxia, and cell colony-formation rate of MDA-MB-231 cells also increased significantly in hypoxia-treated cells. These results encourage the exploration of hypoxia as a mechanism which might not be underestimated in chemo-resistant breast cancer treatment.
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Fetal and Neonatal Surgery, Hunan Children's Hospital, Changsha, Hunan, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhou-yu
authors.initials: ZY
authors.lastname: Ning
authors.affiliation: Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Nanhua University, Hengyang, 421001, Changsha, China. 18607345916@163.com.
authors.forename: Hai-fan
authors.initials: HF
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Xincun Road 389, Shanghai, 200065, China. liujie3131@tongji.edu.cn.
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000473:pathology; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D000072258:Tumor Hypoxia
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018960:Hyaluronan Receptors
keywords: Breast cancer; Cancer stem cells; Hypoxia; Stem cell niche; Stemness