Integrated transcriptomics, proteomics, and functional analysis to characterize the tissue‐specific small extracellular vesicle network of breast cancer
Lesang Shen,
Huanhuan Huang,
Zichen Wei,
Wuzhen Chen,
Jiaxin Li,
Yao Yao,
Jun Zhou,
Jian Liu,
Shanshan Sun,
Wenjie Xia,
Ting Zhang,
Xiuyan Yu,
Jun Shen,
Weilan Wang,
Jingxin Jiang,
Jian Huang,
Ming Jiang,
Chao Ni
Affiliations
Lesang Shen
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Huanhuan Huang
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Zichen Wei
Center for Genetic Medicine The Fourth Affiliated Hospital, Zhejiang University School of Medicine Hangzhou China
Wuzhen Chen
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Jiaxin Li
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Yao Yao
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Jun Zhou
Department of Breast Surgery Affiliated Hangzhou First People's Hospital Zhejiang University Hangzhou China
Jian Liu
Department of Breast Surgery Affiliated Hangzhou First People's Hospital Zhejiang University Hangzhou China
Shanshan Sun
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Wenjie Xia
Department of Breast Surgery Zhejiang Provincial People's Hospital Hangzhou China
Ting Zhang
Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province Second Affiliated Hospital, Zhejiang University Hangzhou China
Xiuyan Yu
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Jun Shen
Department of Surgical Oncology Sir Run Run Shaw Hospital, Zhejiang University Hangzhou China
Weilan Wang
Department of Breast Surgery Changxing People's Hospital Huzhou China
Jingxin Jiang
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Jian Huang
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Ming Jiang
Center for Genetic Medicine The Fourth Affiliated Hospital, Zhejiang University School of Medicine Hangzhou China
Chao Ni
Department of Breast Surgery Second Affiliated Hospital, Zhejiang University Hangzhou China
Abstract Small extracellular vesicles (sEVs) are essential mediators of intercellular communication within the tumor microenvironment (TME). Although the biological features of sEVs have been characterized based on in vitro culture models, recent evidence indicates significant differences between sEVs derived from tissue and those derived from in vitro models in terms of both content and biological function. However, comprehensive comparisons and functional analyses are still limited. Here, we collected sEVs from breast cancer tissues (T‐sEVs), paired normal tissues (N‐sEVs), corresponding plasma (B‐sEVs), and tumor organoids (O‐sEVs) to characterize their transcriptomic and proteomic profiles. We identified the actual cancer‐specific sEV signatures characterized by enriched cell adhesion and immunomodulatory molecules. Furthermore, we revealed the significant contribution of cancer‐associated fibroblasts in the sEV network within the TME. In vitro model‐derived sEVs did not entirely inherit the extracellular matrix‐ and immunity regulation‐related features of T‐sEVs. Also, we demonstrated the greater immunostimulatory ability of T‐sEVs on macrophages and CD8+ T cells compared to O‐sEVs. Moreover, certain sEV biomarkers derived from noncancer cells in the circulation exhibited promising diagnostic potential. This study provides valuable insights into the functional characteristics of tumor tissue‐derived sEVs, highlighting their potential as diagnostic markers and therapeutic agents for breast cancer.
