Biological differences between normal and cancer-associated fibroblasts in breast cancer

Dengdi Hu; Wenying Zhuo; Peirong Gong; Feiyang Ji; Xun Zhang; Yongxia Chen; Misha Mao; Siwei Ju; Yuehong Pan; Jun Shen

Heliyon (Sep 2023)

Biological differences between normal and cancer-associated fibroblasts in breast cancer

Dengdi Hu,
Wenying Zhuo,
Peirong Gong,
Feiyang Ji,
Xun Zhang,
Yongxia Chen,
Misha Mao,
Siwei Ju,
Yuehong Pan,
Jun Shen

Affiliations

Dengdi Hu: Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China
Wenying Zhuo: Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China; Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China; , China (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), China; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, Zhejiang, China
Peirong Gong: Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China
Feiyang Ji: Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China; , China (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), China; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, Zhejiang, China
Xun Zhang: Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China; , China (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), China; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, Zhejiang, China
Yongxia Chen: Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China; , China (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), China; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, Zhejiang, China
Misha Mao: Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China; , China (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), China; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, Zhejiang, China
Siwei Ju: Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China; , China (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), China; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, Zhejiang, China
Yuehong Pan: Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, Zhejiang, China
Jun Shen: Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China; , China (Key Laboratory of Cancer Prevention and Intervention, Ministry of Education), China; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, Zhejiang, China; Corresponding author. Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, No. 3 Eastern Qingchun Road, Hangzhou, 310016, Zhejiang, China.

Journal volume & issue: Vol. 9, no. 9
p. e19803

Abstract

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Background: Cancer-associated fibroblasts (CAFs) constitute the primary constituents of the tumor microenvironment (TME) and exert significant influences on cancer progression. However, adequate comprehension of CAF profiles in breast cancer, as well as the precise mechanisms underlying their promotion of cancer, remains lacking. Objectives: To discerns the biological differences between normal fibroblasts (NFs) and CAFs in breast cancer and explore the underlying mechanism. Methods: Three pairs of CAFs and NFs were isolated from breast cancer patients of diverse subtypes who had not undergone prior radiotherapy or chemotherapy. Morphological characteristics of CAFs and NFs were assessed through optical and electron microscopy, their biological attributes were examined using cell counting kits and transwell assays, and their impact on breast cancer cells was simulated using a coculture system. Furthermore, the miRNA profiles of CAFs and NFs were sequenced via an Illumina HiSeq 2500 platform. Results: CAFs exhibited higher growth rate and motility than NFs and a stronger potential to promote the malignancy of breast cancer cells. RNA sequencing of both NFs and CAFs revealed differentially expressed miRNAs with notable variability among distinct patients within their NFs and CAFs, while the enrichment of the target genes of differentially expressed miRNAs within both GO terms and KEGG pathways demonstrated significant similarity across patients with different profiles. Conclusion: CAFs have greater malignancy and higher potential to influence the growth, migration, invasion and chemoresistance of cocultured breast cancer cells than NFs. In addition, the miRNAs that are differentially expressed in CAFs when compared to NFs display substantial variability across patients with distinct breast cancer subtypes, while the enrichment of target genes regulated by these miRNAs, within GO terms and KEGG pathways, remains remarkably consistent among patients with varying profiles.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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