Abstract
CD44, a cell adhesion protein, involves in various process in cancer such as cell survival and metastasis. Most researches on CD44 in cancer focus on cancer cells. Recently, it is found that CD44 expression is high in fibroblasts of tumour microenvironment. However, its role in communication between fibroblasts and breast cancer cells is seldom known. In this study, CD44‐positive (CD44+Fbs) and CD44‐negative carcinoma‐associated fibroblasts (CD44−Fbs) were isolated and cocultured with breast cancer cells for analysis of cell survival and drug resistance. We found that CD44+Fbs promoted breast cancer cell survival and paclitaxel resistance and inhibited paclitaxel‐induced apoptosis. Our further research for the molecular mechanism showed that IGF2BP3 bound to CD44 mRNA and enhanced CD44 expression, which increased IGF2 levels of fibroblasts and then stimulated breast cancer cell proliferation and drug resistance. IGF2 was found to activate Hedgehog signal pathway in breast cancer cells. In conclusion, the results illustrated that in CD44+Fbs, binding of IGF2BP3 and CD44 promotes IGF2 expression and then accelerates breast cancer cell proliferation, survival and induced chemotherapy resistance likely by activating Hedgehog signal pathways.
Highlights
The tumour microenvironment plays very important roles in the development and progression of cancer
In the period of studying roles of fibroblasts on cancer cells, we found that CD44 expression level was very high in fibroblasts; we suggested that the fibroblasts with high CD44 expression may play important roles in the effect on breast cancer cells
CD44 functions as a member of cell adhesion molecules that is responsible for mediating communication and adhesion between adjacent cells and the extracellular matrix (ECM) [17, 18]
Summary
The tumour microenvironment plays very important roles in the development and progression of cancer. Tumour tissues consist of various cells and non-cell components. The cell components include cancer cells, fibroblasts, endothelial cells, pericytes, immune cells and various bone marrow-derived progenitor cells [1, 2]. Fibroblasts are the most abundant cells in tumour stroma. The activated cancerassociated fibroblasts in the cancer niche build a permissive and supportive microenvironment for tumour development and play important roles in cancer progression including metabolism, metastasis, proliferation, anti-apoptosis, angiogenesis and chemoresistance by interaction with cancer cells or other cells [3,4,5]. Fibroblasts could affect behaviours of cancer cells by activating signal pathways, miRNAs and soluble molecules and so on
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
