CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p
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RESEARCH
Open Access
CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p Lu Wang1†, Guang Yang2†, Danfeng Zhao1, Jiaqi Wang1, Yang Bai1, Qiang Peng1, Hongzhi Wang1, Ruizhe Fang1, Guang Chen1, Zhichao Wang1, Keliang Wang1, Guangbin Li1, Yinhui Yang1, Ziqi Wang1, Pengyu Guo1, Li Peng1, Dayong Hou1 and Wanhai Xu1*
Abstract Background: Clear cell renal cell carcinoma (CCRCC) is characterized by a highly metastatic potential. The stromal communication between stem cells and cancer cells critically influences metastatic dissemination of cancer cells. Methods: The effect of exosomes isolated from cancer stem cells (CSCs) of CCRCC patients on the progress of epithelial-mesenchymal transition (EMT) and lung metastasis of CCRCC cells were examined. Results: CSCs exosomes promoted proliferation of CCRCC cells and accelerated the progress of EMT. Bioactive miR19b-3p transmitted to cancer cells by CSC exosomes induced EMT via repressing the expression of PTEN. CSCs exosomes derived from CCRCC patients with lung metastasis produced the strongest promoting effect on EMT. Notably, CD103+ CSC exosomes were enriched in tumor cells and in lung as well, highlighting the organotropism conferred by CD103. In addition, CD103+ exosomes were increased in blood samples from CCRCC patients with lung metastasis. Conclusions: CSC exosomes transported miR-19b-3p into CCRCC cells and initiated EMT promoting metastasis. CD103+ acted to guide CSC exosomes to target cancer cells and organs, conferring the higher metastatic capacity of CCRCC to lungs, suggesting CD103+ exosomes as a potential metastatic diagnostic biomarker. Keywords: Cancer stem cells, miR-19b-3p, Epithelial-mesenchymal transition, CD103+ exosomes, Lung metastasis
Background Renal carcinoma is among the 10 most common cancers, representing 3.7% of all new cancer cases. The incidence has been kept rising worldwide and the prognosis remains poor. Clear cell renal cell carcinoma (CCRCC), a renal cortical tumor characterized by malignant epithelial cells, is the most common type of renal carcinomas, constituting 80% of all cases. Over 30% of patients present with metastasis at the time of diagnosis [1–3]. Cancer stem cell (CSC) is a critical factor during CCRCC development because it promotes metastatic * Correspondence: [email protected] † Lu Wang and Guang Yang contributed equally to this work. 1 Department of Urology (Heilongjiang Key Laboratory of Scientific Research in Urology), the Fourth Hospital of Harbin Medical University, No. 37 Yi-Yuan Street, Nangang District, Harbin, Heilongjiang Province 150081, People’s Republic of China Full list of author information is available at the end of the article
spread [4]. CCRCC stem cells (CCRCC-CSCs) express marker gene CD105 and stem cell markers Nestin, Nanog, and Oct-3/4. Despite successful isolation of CSCs in 2008, insufficient progress has been made towards decoding the roles of CSCs governing CCRCC development in the past decade [5]. It is of paramount importance to underst
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