Junction Plakoglobin Facilitates Angiogenesis in Melanoma
Katie M. Leick*, Robin Lindsay*, Mahmut Parlak*, Tarek Abbas*, Victor H Engelhard*, Craig L. Slingluff, Jr.
University of Virginia, Charlottesville, VA
Introduction: We have previously reported that overexpression junction plakoglobin (JUP) is associated with poor survival and decreased immune infiltration in human melanoma and that selective overexpression in B16 melanoma enhances tumor growth. We hypothesized that the tumor-promoting effect of JUP was due either to suppression of immune function or more direct enhancement of tumor growth. To explore possible mediators of immune function and angiogenesis, we evaluated the effect of JUP overexpression on these mediators in the B16 melanoma microenvironment.
Methods: JUP overexpression was induced by lentiviral transduction of murine B16-AAD melanoma cells, which were implanted intraperitoneally along with untransfected control tumors, then harvested at day 14, and cell lysis and protein estimation were performed. Concentrations of 27 cytokines chemokines were measured with the Meso Scale Discovery Assay. Correcting for multiple comparisons, p values of less than 0.005 were considered significant.
Results: Overexpression of JUP in murine B16-AAD melanoma resulted in no significant changes in most of the tested cytokines and chemokines. However, the analyses revealed significantly higher concentrations of VEGF (p=0.0026) and lower levels of IL-33 (p < 0.0001) compared to control.
Conclusions: JUP overexpression is associated with high VEGF and low IL-33 in melanoma in vivo, raising the possibility of enhanced angiogenesis. Therefore, identification of regulatory targets of JUP may enable intervention on its expression to confer clinical benefit.
* By Invitation
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