Exosomic microRNAs in the Tumor Microenvironment

Dissecting the crosstalk between tumor cells and tumor microenvironment is quickly becoming the new frontier in cancer research. It is now widely accepted that cancer cells can exert a profound influence over their surroundings, by changing the microenvironment from a normal to a tumor-supportive state that allows for sustained tumor growth, invasion, and drug resistance. Extracellular vesicles, especially exosomes, are recognized as a new category of intercellular communicator, and they are emerging as of primary importance in controlling the interplay between the tumor and its environment. Exosomes derived from cancer cells or from cells of the tumor microenvironment allow for the horizontal transfer of information by virtue of their cargo, made of functional proteins and nucleic acids that are specifically sorted and loaded in exosomes during their biogenesis. In this review, we will discuss the current knowledge regarding the role invested by microRNAs, a family of short non-coding RNAs frequently deregulated in malignancies and present in exosomes, in shaping the microenvironment in a cancer-dependent manner.

[1]  D. Amadori,et al.  Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy. , 2015, Journal of the National Cancer Institute.

[2]  D. Banerjee,et al.  Regulation of the inflammatory profile of stromal cells in human breast cancer: prominent roles for TNF-α and the NF-κB pathway , 2015, Stem Cell Research & Therapy.

[3]  T. Tomita,et al.  FGF9 from cancer-associated fibroblasts is a possible mediator of invasion and anti-apoptosis of gastric cancer cells , 2015, BMC Cancer.

[4]  Hong-Jian Zhu,et al.  Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression. , 2015, Seminars in cell & developmental biology.

[5]  A. Larue,et al.  Hematopoietic stem cell-derived adipocytes and fibroblasts in the tumor microenvironment. , 2015, World journal of stem cells.

[6]  A. Noël,et al.  Endothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer , 2015, Oncotarget.

[7]  Y. Mo,et al.  Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA, proteins, and metabolites , 2014, Oncotarget.

[8]  K. Ohyashiki,et al.  Exosomal miR-135b shed from hypoxic multiple myeloma cells enhances angiogenesis by targeting factor-inhibiting HIF-1. , 2014, Blood.

[9]  Yue-Qin Chen,et al.  Circulating miRNAs in cancer: from detection to therapy , 2014, Journal of Hematology & Oncology.

[10]  J. Lieberman,et al.  miR-200-containing extracellular vesicles promote breast cancer cell metastasis. , 2014, The Journal of clinical investigation.

[11]  Y. Mo,et al.  Exosome-mediated transfer of miR-10b promotes cell invasion in breast cancer , 2014, Molecular Cancer.

[12]  George A Calin,et al.  Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. , 2014, Cancer cell.

[13]  G. Calin,et al.  The fusion of two worlds: Non-coding RNAs and extracellular vesicles - diagnostic and therapeutic implications (Review) , 2014, International journal of oncology.

[14]  F. Sánchez‐Madrid,et al.  Sorting it out: regulation of exosome loading. , 2014, Seminars in cancer biology.

[15]  Mark Ibberson,et al.  Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. , 2014, Cell reports.

[16]  M. Fabbri,et al.  microRNAs in the tumor microenvironment: solving the riddle for a better diagnostics , 2014, Expert review of molecular diagnostics.

[17]  C. Croce,et al.  Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7 , 2014, Proceedings of the National Academy of Sciences.

[18]  M. Junttila,et al.  Influence of tumour micro-environment heterogeneity on therapeutic response , 2013, Nature.

[19]  M. Zöller,et al.  Exosomal tumor microRNA modulates premetastatic organ cells. , 2013, Neoplasia.

[20]  Graça Raposo,et al.  Extracellular vesicles: Exosomes, microvesicles, and friends , 2013, The Journal of cell biology.

[21]  Yuquan Wei,et al.  Prognostic Significance of Tumor-Associated Macrophages in Solid Tumor: A Meta-Analysis of the Literature , 2012, PloS one.

[22]  M. Rubin,et al.  Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. , 2012, The American journal of pathology.

[23]  Roberta Galli,et al.  MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response , 2012, Proceedings of the National Academy of Sciences.

[24]  T. Golub,et al.  Tumor microenvironment induces innate RAF-inhibitor resistance through HGF secretion , 2012, Nature.

[25]  P. Workman,et al.  Discovery of small molecule cancer drugs: Successes, challenges and opportunities , 2012, Molecular oncology.

[26]  F. Su,et al.  Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells , 2011, Molecular Cancer.

[27]  Karin Jirström,et al.  Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. , 2011, Cancer discovery.

[28]  H. Komatsu.  [Antibody therapy in cancer]. , 2010, Nihon rinsho. Japanese journal of clinical medicine.

[29]  J. Xiang,et al.  Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes. , 2006, Experimental oncology.

[30]  Kristian Pietras,et al.  High interstitial fluid pressure — an obstacle in cancer therapy , 2004, Nature Reviews Cancer.

[31]  Hanlin Gao,et al.  UC Office of the President Recent Work Title Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis , 2014 .

[32]  Peng Guan,et al.  Oncotargets and Therapy Dovepress , 2022 .