Stem Cell Exosomes Inhibit Angiogenesis and Tumor Growth of Oral Squamous Cell Carcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2019 Jan 26

PMID 30679544

Citations 70

Authors

Leonie Rosenberger

Marcelo Ezquer

Fernando Lillo-Vera

Paulina L Pedraza

Maria Ignacia Ortuzar

Paz L Gonzalez

Aliosha I Figueroa-Valdes

Jimena Cuenca

Fernando Ezquer

Maroun Khoury

Francisca Alcayaga-Miranda

Affiliations

Soon will be listed here.

Abstract

Recently, exosomes secreted by menstrual mesenchymal stem cells have been identified as inhibitory agents of tumor angiogenesis and modulators of the tumor cell secretome in prostate and breast cancer. However, their direct effect on endothelial cells and paracrine mediators have not yet been investigated. Using a carrier-based cell culture system to test the scalability for exosome production, we showed that different types of endothelial cells present specific kinetics for exosomes internalization. Exosome-treatment of endothelial cells increased cytotoxicity and reduced VEGF secretion and angiogenesis in a dose-dependent manner. Using the hamster buccal pouch carcinoma as a preclinical model for human oral squamous cell carcinoma, we demonstrated a significant antitumor effect of intra-tumoral injection of exosomes associated with a loss of tumor vasculature. These results address up-scaling of exosome production, a relevant issue for their clinical application, and also assess menstrual stem cell exosomes as potential anti-angiogenic agents for the treatment of neoplastic conditions.

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References

Girling J, Rogers P . Recent advances in endometrial angiogenesis research. Angiogenesis. 2005; 8(2):89-99. DOI: 10.1007/s10456-005-9006-9. View

Bruno S, Collino F, Deregibus M, Grange C, Tetta C, Camussi G . Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth. Stem Cells Dev. 2012; 22(5):758-71. DOI: 10.1089/scd.2012.0304. View

Thery C, Zitvogel L, Amigorena S . Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002; 2(8):569-79. DOI: 10.1038/nri855. View

Gacche R . Compensatory angiogenesis and tumor refractoriness. Oncogenesis. 2015; 4:e153. PMC: 4753522. DOI: 10.1038/oncsis.2015.14. View

Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A . Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem. 2009; 284(49):34211-22. PMC: 2797191. DOI: 10.1074/jbc.M109.041152. View

Ezquer M, Urzua C, Montecino S, Leal K, Conget P, Ezquer F . Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice. Stem Cell Res Ther. 2016; 7:42. PMC: 4793534. DOI: 10.1186/s13287-016-0299-y. View

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4):315-7. DOI: 10.1080/14653240600855905. View

Alcayaga-Miranda F, Varas-Godoy M, Khoury M . Harnessing the Angiogenic Potential of Stem Cell-Derived Exosomes for Vascular Regeneration. Stem Cells Int. 2016; 2016:3409169. PMC: 4834153. DOI: 10.1155/2016/3409169. View

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

10.

Bruna F, Arango-Rodriguez M, Plaza A, Espinoza I, Conget P . The administration of multipotent stromal cells at precancerous stage precludes tumor growth and epithelial dedifferentiation of oral squamous cell carcinoma. Stem Cell Res. 2016; 18:5-13. DOI: 10.1016/j.scr.2016.11.016. View

11.

Thery C . Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep. 2011; 3:15. PMC: 3155154. DOI: 10.3410/B3-15. View

12.

Shabbir A, Cox A, Rodriguez-Menocal L, Salgado M, Van Badiavas E . Mesenchymal Stem Cell Exosomes Induce Proliferation and Migration of Normal and Chronic Wound Fibroblasts, and Enhance Angiogenesis In Vitro. Stem Cells Dev. 2015; 24(14):1635-47. PMC: 4499790. DOI: 10.1089/scd.2014.0316. View

13.

Mulcahy L, Pink R, Carter D . Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 2014; 3. PMC: 4122821. DOI: 10.3402/jev.v3.24641. View

14.

Horibe S, Tanahashi T, Kawauchi S, Murakami Y, Rikitake Y . Mechanism of recipient cell-dependent differences in exosome uptake. BMC Cancer. 2018; 18(1):47. PMC: 5756423. DOI: 10.1186/s12885-017-3958-1. View

15.

Wiklander O, Nordin J, OLoughlin A, Gustafsson Y, Corso G, Mager I . Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015; 4:26316. PMC: 4405624. DOI: 10.3402/jev.v4.26316. View

16.

Kyzas P, Cunha I, Ioannidis J . Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res. 2005; 11(4):1434-40. DOI: 10.1158/1078-0432.CCR-04-1870. View

17.

Alcayaga-Miranda F, Cuenca J, Martin A, Contreras L, Figueroa F, Khoury M . Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis. Stem Cell Res Ther. 2015; 6:199. PMC: 4609164. DOI: 10.1186/s13287-015-0192-0. View

18.

Nagini S . Of humans and hamsters: the hamster buccal pouch carcinogenesis model as a paradigm for oral oncogenesis and chemoprevention. Anticancer Agents Med Chem. 2009; 9(8):843-52. DOI: 10.2174/187152009789124619. View

19.

Nagini S, Letchoumy P, A T, Cr R . Of humans and hamsters: a comparative evaluation of carcinogen activation, DNA damage, cell proliferation, apoptosis, invasion, and angiogenesis in oral cancer patients and hamster buccal pouch carcinomas. Oral Oncol. 2009; 45(6):e31-7. DOI: 10.1016/j.oraloncology.2009.01.006. View

20.

Lai R, Arslan F, Lee M, Sze N, Choo A, Chen T . Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010; 4(3):214-22. DOI: 10.1016/j.scr.2009.12.003. View