scholarly journals Novel C‐terminal heat shock protein 90 inhibitors target breast cancer stem cells and block migration, self‐renewal, and epithelial–mesenchymal transition

2020 ◽  
Vol 14 (9) ◽  
pp. 2058-2068
Author(s):  
Chitra Subramanian ◽  
Patrick T. Grogan ◽  
Ton Wang ◽  
Joseph Bazzill ◽  
Ang Zuo ◽  
...  
PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4805 ◽  
Author(s):  
Bixiao Wang ◽  
Chunfang Xi ◽  
Mingwei Liu ◽  
Haichen Sun ◽  
Shuang Liu ◽  
...  

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 (α-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.


2011 ◽  
Vol 71 (13) ◽  
pp. 4707-4719 ◽  
Author(s):  
Michael K. Asiedu ◽  
James N. Ingle ◽  
Marshall D. Behrens ◽  
Derek C. Radisky ◽  
Keith L. Knutson

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150407 ◽  
Author(s):  
Naiane do Nascimento Gonçalves ◽  
Jucimara Colombo ◽  
Juliana Ramos Lopes ◽  
Gabriela Bottaro Gelaleti ◽  
Marina Gobbe Moschetta ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kai Song ◽  
Maryam Farzaneh

AbstractBreast cancer is the second common cancer and the leading cause of malignancy among females overall. Breast cancer stem cells (BCSCs) are a small population of breast cancer cells that play a critical role in the metastasis of breast cancer to other organs in the body. BCSCs have both self-renewal and differentiation capacities, which are thought to contribute to the aggressiveness of metastatic lesions. Therefore, targeting BCSCs can be a suitable approach for the treatment and metastasis of breast cancer. Growing evidence has indicated that the Wnt, NFκB, Notch, BMP2, STAT3, and hedgehog (Hh) signaling pathways govern epithelial-to-mesenchymal transition (EMT) activation, growth, and tumorigenesis of BCSCs in the primary regions. miRNAs as the central regulatory molecules also play critical roles in BCSC self-renewal, metastasis, and drug resistance. Hence, targeting these pathways might be a novel therapeutic approach for breast cancer diagnosis and therapy. This review discusses known signaling mechanisms involved in the stimulation or prevention of BCSC self-renewal, metastasis, and tumorigenesis.


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