机构：[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China普通外科首都医科大学宣武医院[2]Department of Breast Surgery, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, China[3]State Key Laboratory of Proteomics, National Center for Protein Sciences, Beijing Proteome Research Center, Beijing, China[4]Surgery Lab, Xuanwu Hospital, Capital Medical University, Beijing, China首都医科大学宣武医院
Background: Breast cancer stem cells (BCSCs) are associated with the invasion of breast cancer. In recent years, studies have demonstrated different phenotypes among BCSCs. Furthermore, BCSCs of diverse phenotypes are present at different tumour sites and different histological stages. Fibroblasts are involved in the phenotypic transformation of BCSCs. Cancer-associated fibroblasts (CAFs) participate in the induction of epithelial-mesenchymal transition, thereby promoting the acquisition of stem cell characteristics, but little is known about the role of normal fibroblasts (NFs) in the phenotypic transformation of BCSCs or about the effect of CAFs and NFs on BCSC phenotypes. Methods: A total of six pairs of primary CAFs and NFs were isolated from surgical samples of breast cancer patients and subjected to morphological, immunohistochemical, cell invasion and proteomics analyses. After establishing a cell culture system with conditioned medium from CAFs and NFs, we used the mammosphere formation assay to explore the effect of CAFs and NFs on the self-renewal ability of BCSCs. The effect of CAFs and NFs on the phenotypic differentiation of BCSCs was further analysed by flow cytometry and immunofluorescence. Results: The isolated CAFs and NFs did not show significant differences in cell morphology or alpha-smooth muscle actin (alpha-SMA) expression, but cell invasion and proteomics analyses demonstrated heterogeneity among these fibroblasts. Both CAFs and NFs could promote the generation of BCSCs, but CAFs displayed a greater ability than NFs in promoting mammosphere formation. Conditioned medium from CAFs increased the proportion of aldehyde dehydrogenase-1 positive (ALDH1(+)) BCSCs, but conditioned medium from NFs was more likely to promote the generation of CD44(+)CD24(-) BCSCs from MCF-7 cells. Discussion: This study validated the heterogeneity among CAFs and NFs and expanded on the conclusion that fibroblasts promote the generation of cancer stem cells. Our results particularly emphasized the effect of NFs on the phenotypic transformation of BCSCs. In addition, this study further highlighted the roles of CAFs and NFs in the induction of different phenotypes in BCSCs.
基金：
This work was supported by the National Natural Science Foundation of China
(No. 81172517) and Beijing Breast Prevention Institute of Breast Cancer Prevention
and Treatment Research Fund
第一作者机构：[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Bixiao Wang,Chunfang Xi,Mingwei Liu,et al.Breast fibroblasts in both cancer and normal tissues induce phenotypic transformation of breast cancer stem cells: a preliminary study[J].PEERJ.2018,6(MAY):e4805.doi:10.7717/peerj.4805.
APA：
Bixiao Wang,Chunfang Xi,Mingwei Liu,Haichen Sun,Shuang Liu...&Hua Kang.(2018).Breast fibroblasts in both cancer and normal tissues induce phenotypic transformation of breast cancer stem cells: a preliminary study.PEERJ,6,(MAY)
MLA：
Bixiao Wang,et al."Breast fibroblasts in both cancer and normal tissues induce phenotypic transformation of breast cancer stem cells: a preliminary study".PEERJ 6..MAY(2018):e4805
