Growth hormone upregulates mediators of melanoma drug efflux and epithelial-to-mesenchymal transition in vitro and in vivo
Growth hormone (GH) and the GH receptor (GHR) are expressed in a wide range of malignant tumors including melanoma. However, the effect of GH/insulin-like growth factor (IGF) on melanoma in vivo has not yet been elucidated. Here we assessed the physical and molecular effects of GH on mouse melanoma B16-F10 and human melanoma SK-MEL-30 cells in vitro. We then corroborated these observations with syngeneic B16-F10 tumors in two mouse lines with different levels of GH/IGF: bovine GH transgenic mice (bGH; high GH, high IGF-1) and GHR gene-disrupted or knockout mice (GHRKO; high GH, low IGF-1). In vitro, GH treatment enhanced mouse and human melanoma cell growth, drug retention and cell invasion. While the in vivo tumor size was unaffected in both bGH and GHRKO mouse lines, multiple drug-efflux pumps were up regulated. This intrinsic capacity of therapy resistance appears to be GH dependent. Additionally, epithelial-to-mesenchymal transition (EMT) gene transcription markers were significantly upregulated in vivo supporting our current and recent in vitro observations. These syngeneic mouse melanoma models of differential GH/IGF action can be valuable tools in screening for therapeutic options where lowering GH/IGF-1 action is important.
Qian, Yanrong; Basu, Reetobrata; Mathes, Samuel C.; Arnett, Nathan A.; Duran-Ortiz, Silvana; Funk, Kevin R.; Brittain, Alison L.; Kulkarni, Prateek; Terry, Joseph C.; Davis, Emily; Singerman, Jordyn T.; Henry, Brooke E.; List, Edward O.; Berryman, Darlene E.; and Kopchick, John J., "Growth hormone upregulates mediators of melanoma drug efflux and epithelial-to-mesenchymal transition in vitro and in vivo" (2020). Edison Biotechnology Institute Open Access Publications. 7.