Kulkarni, P.; Basu, R.; Bonn, T.; Low, B.; Mazurek, N.; Kopchick, J. Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma Derived Exosomes. Preprints2024, 2024070052. https://doi.org/10.20944/preprints202407.0052.v1
APA Style
Kulkarni, P., Basu, R., Bonn, T., Low, B., Mazurek, N., & Kopchick, J. (2024). Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma Derived Exosomes. Preprints. https://doi.org/10.20944/preprints202407.0052.v1
Chicago/Turabian Style
Kulkarni, P., Nathaniel Mazurek and John Kopchick. 2024 "Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma Derived Exosomes" Preprints. https://doi.org/10.20944/preprints202407.0052.v1
Abstract
Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin and MMP2, enhancing drug resistance and migration in recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights to the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
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