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Role of GRM1 in exosome production and melanoma metastasis
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Isola, Allison L.. Role of GRM1 in exosome production and melanoma metastasis. Retrieved from https://doi.org/doi:10.7282/T3GX4FPM

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TitleRole of GRM1 in exosome production and melanoma metastasis
NameIsola, Allison L. (author); Zarbl, Helmut (chair); Chen, Suzie (internal member); White, Lori A (internal member); Furmanski, Philip (internal member); Goydos, James S (outside member); Rutgers University; School of Graduate Studies
Date Created2017
Other Date2017-10 (degree)
SubjectToxicology, Melanoma
Extent1 online resource (x, 119 p. : ill.)
DescriptionExosomes are naturally occurring membrane-bound nanovesicles generated constitutively and released by various cell types, and often in higher quantities by tumor cells. Exosomes have been postulated to 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. Earlier studies showed that genetic modulation in GRM1 expression by siRNA or disruption of GRM1-mediated glutamate signaling by pharmacological inhibitors interfering with downstream effectors resulting in a decrease in both cell proliferation in vitro and tumor progression in vivo, suggesting that active GRM1 may participate in melanomagenesis in our system. The overall goal of this dissertation is to determine whether the presence and activation of GRM1 plays a role in exosome formation, and subsequent tumor development and progression. To test this, the first aim utilized in vitro cultured cells in which GRM1 expression and function were modulated by pharmacological and genetic means and consequences on exosome production by such manipulations were evaluated in vitro. We also assessed if exosomes derived from GRM1 expressing melanoma cells promote cell growth, migration, invasion as well as colony formation under anchorage-independent growth condition of GRM1 negative cells. Results showed that GRM1 expression in cells, per se, did not modulate exosome quantity, however, modified the qualities and functions of these exosomes. In Aim 2 we used riluzole, a glutamate signaling blockade, in a melanoma prone mouse model (TGS) for the in vivo assessment of exosomal quantity and quality. Daily treatment of TGS mice with riluzole had no detectable effect on the quantity of exosomes in circulation, however riluzole treatment influenced the effects of the circulating exosomes on metastatic behavior of recipient cells.
NotePh.D.
NoteIncludes bibliographical references
Noteby Allison L. Isola
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T3GX4FPM
Languageeng
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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