Oncotarget

Research Papers:

Exosomes released by metabotropic glutamate receptor 1 (GRM1) expressing melanoma cells increase cell migration and invasiveness

Allison L. Isola, Kevinn Eddy, Krzysztof Zembrzuski, James S. Goydos and Suzie Chen _

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Oncotarget. 2018; 9:1187-1199. https://doi.org/10.18632/oncotarget.23455

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Abstract

Allison L. Isola1,2, Kevinn Eddy1, Krzysztof Zembrzuski1, James S. Goydos3 and Suzie Chen1,2,3

1Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University, Piscataway, NJ 08854, USA

2Joint Graduate Program in Toxicology, Rutgers, The State University, Piscataway, NJ 08854, USA

3Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA

Correspondence to:

Suzie Chen, email: [email protected]

Keywords: exosomes; GPCR; melanoma; GRM1; cancer

Received: May 10, 2017     Accepted: December 08, 2017     Published: December 19, 2017

ABSTRACT

Exosomes are naturally occurring membrane-bound nanovesicles generated constitutively and released by various cell types, and often in higher quantities by tumor cells. Exosomes may facilitate communication between the primary tumor and its local microenvironment, supporting cell invasion and other early events in metastasis. A neuronal receptor, metabotropic glutamate receptor 1 (GRM1), when ectopically expressed in melanocytes, induces in vitro melanocytic transformation and spontaneous malignant melanoma development in vivo in a transgenic mouse model. Our earlier studies showed that genetic modulation in GRM1 expression by siRNA or disruption of GRM1-mediated glutamate signaling interfere with downstream effectors resulting in a decrease in both cell proliferation in vitro and tumor progression in vivo. In this study, we sought to determine whether exosome formation might play a role in GRM1 mediated melanoma development and progression. To test this, we utilized in vitro cultured cells in which GRM1 expression and function could be modulated by pharmacological and genetic means and determined effects on exosome production. We also tested the effects of exosomes from GRM1 expressing melanoma cells on growth, migration and invasion of GRM1 negative cells. Our results show that although GRM1 expression has no influence on exosome quantity, exosomes produced by GRM1-positive cells modulate the ability of the recipient cell to migrate, invade and exhibit anchorage-independent cell growth.


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