Cancer-associated fibroblasts from invasive breast cancer have an attenuated capacity to secrete collagens

Fu,Zhixuan; Song,Peiming; Li,Dongbo; Yi,Chenghao; Chen,Huarong; Ruan,Shuqin; Shi,Zhong; Xu,Wenhong; Fu,Xianhua; Zheng,Shu

doi:10.3892/ijo.2014.2562

Cancer-associated fibroblasts from invasive breast cancer have an attenuated capacity to secrete collagens

Authors:
- Zhixuan Fu
- Peiming Song
- Dongbo Li
- Chenghao Yi
- Huarong Chen
- Shuqin Ruan
- Zhong Shi
- Wenhong Xu
- Xianhua Fu
- Shu Zheng
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Affiliations: Key Laboratory of Cancer Prevention and Intervention (China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Cardiovascular Ward of Geriatric Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: July 25, 2014 https://doi.org/10.3892/ijo.2014.2562
Pages: 1479-1488

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Abstract

Normal fibroblasts produce extracellular matrix (ECM) components that form the structural framework of tissues. Cancer-associated fibroblasts (CAFs) with an activated phenotype mainly contribute to ECM deposition and construction of cancer masses. However, the stroma of breast cancer tissues has been shown to be more complicated, and the mechanisms through which CAFs influence ECM deposition remain elusive. In this study, we found that the activated fibroblast marker α-smooth muscle actin (α-SMA) was only present in the stroma of breast cancer tissue, and the CAFs isolated from invasive breast cancer sample remained to be activated and proliferative in passages. To further assess the difference between CAFs and normal breast fibroblasts (NFs), MALDI TOF/TOF‑MS was used to analyze the secretory proteins of primary CAFs and NFs. In total, 2,903 and 3,023 proteins were identified. Mass spectrum quantitative assay and data analysis for extracellular proteins indicated that the CAFs produce less collagens and matrix-degrading enzymes compared with NFs. This finding was confirmed by western blot analysis. Furthermore, we discovered that reduced collagen deposition was present in the stroma of invasive breast cancer. These studies showed that although CAFs from invasive breast cancer possess an activated phenotype, they secreted less collagen and induced less ECM deposition in cancer stroma. In cancer tissue, the remodeling of stromal structure and tumor microenvironment might, therefore, be attributed to the biological changes in CAFs including their protein expression profile.

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