Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT

Autor: Buqing Sai, Guiyuan Li, Lujuan Wang, Leliang Zheng, Yuhui Wang, Juanjuan Xiang, Jingqun Tang, Xina Zhang, Fan Wang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Lung Neoplasms
Apoptosis
BMSCs
exosomal miRNA
Exosomes
Metastasis
STAT3
Mice
0302 clinical medicine
Cell Movement
Tumor Cells
Cultured
Hypoxia
EMT
Middle Aged
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Gene Expression Regulation
Neoplastic
Survival Rate
Oncology
030220 oncology & carcinogenesis
Molecular Medicine
Female
Signal Transduction
STAT3 Transcription Factor
Stromal cell
Epithelial-Mesenchymal Transition
Mice
Nude
Biology
lcsh:RC254-282
03 medical and health sciences
microRNA
medicine
Biomarkers
Tumor
Animals
Humans
Lung cancer
Cell Proliferation
Research
Mesenchymal stem cell
Mesenchymal Stem Cells
medicine.disease
Xenograft Model Antitumor Assays
Microvesicles
Mice
Inbred C57BL
MicroRNAs
030104 developmental biology
Case-Control Studies
Cancer cell
Cancer research
biology.protein
Follow-Up Studies
Zdroj: Molecular Cancer, Vol 18, Iss 1, Pp 1-15 (2019)
Molecular Cancer
ISSN: 1476-4598
Popis: Background Metastasis is the main cause of lung cancer mortality. Bone marrow-derived mesenchymal stem cells (BMSCs) are a component of the cancer microenvironment and contribute to cancer progression. Intratumoral hypoxia affects both cancer and stromal cells. Exosomes are recognized as mediators of intercellular communication. Here, we aim to further elucidate the communication between BMSC-derived exosomes and cancer cells in the hypoxic niche. Methods Exosomal miRNA profiling was performed using a microRNA array. Lung cancer cells and an in vivo mouse syngeneic tumor model were used to evaluate the effects of select exosomal microRNAs. Hypoxic BMSC-derived plasma exosomal miRNAs were assessed for their capacity to discriminate between cancer patients and non-cancerous controls and between cancer patients with or without metastasis. Results We demonstrate that exosomes derived from hypoxic BMSCs are taken by neighboring cancer cells and promote cancer cell invasion and EMT. Exosome-mediated transfer of select microRNAs, including miR-193a-3p, miR-210-3p and miR-5100, from BMSCs to epithelial cancer cells activates STAT3 signaling and increases the expression of mesenchymal related molecules. The diagnostic accuracy of individual microRNA showed that plasma exosomal miR-193a-3p can discriminate cancer patients from non-cancerous controls. A panel of these three plasma exosomal microRNAs showed a better diagnostic accuracy to discriminate lung cancer patients with or without metastasis than individual exosomal microRNA. Conclusions Exosome-mediated transfer of miR-193a-3p, miR-210-3p and miR-5100, could promote invasion of lung cancer cells by activating STAT3 signalling-induced EMT. These exosomal miRNAs may be promising noninvasive biomarkers for cancer progression. Electronic supplementary material The online version of this article (10.1186/s12943-019-0959-5) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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