Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Dec 24

PMID 34943937

Citations 24

Authors

Aisling Forder

Chi-Yun Hsing

Jessica Trejo Vazquez

Cathie Garnis

Affiliations

Soon will be listed here.

Abstract

Communication between cancer cells and the surrounding stromal cells of the tumor microenvironment (TME) plays a key role in promoting metastasis, which is the major cause of cancer death. Small membrane-bound particles called extracellular vesicles (EVs) are released from both cancer and stromal cells and have a key role in mediating this communication through transport of cargo such as various RNA species (mRNA, miRNA, lncRNA), proteins, and lipids. Tumor-secreted EVs have been observed to induce a pro-tumorigenic phenotype in non-malignant cells of the stroma, including fibroblasts, endothelial cells, and local immune cells. These cancer-associated cells then drive metastasis by mechanisms such as increasing the invasiveness of cancer cells, facilitating angiogenesis, and promoting the formation of the pre-metastatic niche. This review will cover the role of EV-mediated signaling in the TME during metastasis and highlight the therapeutic potential of targeting these pathways to develop biomarkers and novel treatment strategies.

Citing Articles

Biogenesis and functional implications of extracellular vesicles in cancer metastasis.

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References

Fang L, Li H, Wang L, Hu J, Jin T, Wang J . MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression. Oncotarget. 2014; 5(10):2974-87. PMC: 4102784. DOI: 10.18632/oncotarget.1614. View

Ong M, B Schofield J . Assessment of lymph node involvement in colorectal cancer. World J Gastrointest Surg. 2016; 8(3):179-92. PMC: 4807319. DOI: 10.4240/wjgs.v8.i3.179. View

Kruger-Genge A, Blocki A, Franke R, Jung F . Vascular Endothelial Cell Biology: An Update. Int J Mol Sci. 2019; 20(18). PMC: 6769656. DOI: 10.3390/ijms20184411. View

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

Luga V, Zhang L, Viloria-Petit A, Ogunjimi A, Inanlou M, Chiu E . Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell. 2012; 151(7):1542-56. DOI: 10.1016/j.cell.2012.11.024. View

Wu M, Ma M, Tan Z, Zheng H, Liu X . Neutrophil: A New Player in Metastatic Cancers. Front Immunol. 2020; 11:565165. PMC: 7546851. DOI: 10.3389/fimmu.2020.565165. View

Wu J, Gao W, Tang Q, Yu Y, You W, Wu Z . M2 Macrophage-Derived Exosomes Facilitate HCC Metastasis by Transferring α β Integrin to Tumor Cells. Hepatology. 2020; 73(4):1365-1380. PMC: 8360085. DOI: 10.1002/hep.31432. View

Huebner K, Prochazka J, Monteiro A, Mahadevan V, Schneider-Stock R . The activating transcription factor 2: an influencer of cancer progression. Mutagenesis. 2019; 34(5-6):375-389. PMC: 6923166. DOI: 10.1093/mutage/gez041. View

Mi X, Xu R, Hong S, Xu T, Zhang W, Liu M . M2 Macrophage-Derived Exosomal lncRNA AFAP1-AS1 and MicroRNA-26a Affect Cell Migration and Metastasis in Esophageal Cancer. Mol Ther Nucleic Acids. 2020; 22:779-790. PMC: 7595846. DOI: 10.1016/j.omtn.2020.09.035. View

10.

Bebelman M, Smit M, Pegtel D, Baglio S . Biogenesis and function of extracellular vesicles in cancer. Pharmacol Ther. 2018; 188:1-11. DOI: 10.1016/j.pharmthera.2018.02.013. View

11.

Yang S, Ma S, Dou H, Liu F, Zhang S, Jiang C . Breast cancer-derived exosomes regulate cell invasion and metastasis in breast cancer via miR-146a to activate cancer associated fibroblasts in tumor microenvironment. Exp Cell Res. 2020; 391(2):111983. DOI: 10.1016/j.yexcr.2020.111983. View

12.

Yan L, Wang P, Fang W, Liang C . Cancer-associated fibroblasts-derived exosomes-mediated transfer of LINC00355 regulates bladder cancer cell proliferation and invasion. Cell Biochem Funct. 2019; 38(3):257-265. DOI: 10.1002/cbf.3462. View

13.

Pang W, Su J, Wang Y, Feng H, Dai X, Yuan Y . Pancreatic cancer-secreted miR-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts. Cancer Sci. 2015; 106(10):1362-9. PMC: 4638007. DOI: 10.1111/cas.12747. View

14.

Chen J, Fei X, Wang J, Cai Z . Tumor-derived extracellular vesicles: Regulators of tumor microenvironment and the enlightenment in tumor therapy. Pharmacol Res. 2020; 159:105041. DOI: 10.1016/j.phrs.2020.105041. View

15.

Richards K, Zeleniak A, Fishel M, Wu J, Littlepage L, Hill R . Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene. 2016; 36(13):1770-1778. PMC: 5366272. DOI: 10.1038/onc.2016.353. View

16.

Zhang Y, Luo G, You S, Zhang L, Liang C, Chen X . Exosomal LINC00355 derived from cancer-associated fibroblasts promotes bladder cancer cell proliferation and invasion by regulating miR-15a-5p/HMGA2 axis. Acta Biochim Biophys Sin (Shanghai). 2021; 53(6):673-682. DOI: 10.1093/abbs/gmab041. View

17.

Pasqualini R, Ruoslahti E . Organ targeting in vivo using phage display peptide libraries. Nature. 1996; 380(6572):364-6. DOI: 10.1038/380364a0. View

18.

Ma Y, Dong S, Li X, Kim B, Yang Z, Jiang W . Extracellular Vesicles: An Emerging Nanoplatform for Cancer Therapy. Front Oncol. 2021; 10:606906. PMC: 7897670. DOI: 10.3389/fonc.2020.606906. View

19.

Li Y, Tao Y, Gao S, Li P, Zheng J, Zhang S . Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p. EBioMedicine. 2018; 36:209-220. PMC: 6197737. DOI: 10.1016/j.ebiom.2018.09.006. View

20.

Baker C, Kedar D, McCarty M, Tsan R, Weber K, Bucana C . Blockade of epidermal growth factor receptor signaling on tumor cells and tumor-associated endothelial cells for therapy of human carcinomas. Am J Pathol. 2002; 161(3):929-38. PMC: 1867249. DOI: 10.1016/S0002-9440(10)64253-8. View