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Human Plasmacytoid Dendritic Cells and Cutaneous Melanoma
Open AccessArticle

A Potential Role of RUNX2- RUNT Domain in Modulating the Expression of Genes Involved in Bone Metastases: An In Vitro Study with Melanoma Cells

1
Department of Medicine, University of Verona, University of Verona, 37100 Verona, Italy
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Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37100 Verona, Italy
3
Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, 37100 Verona, Italy
*
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 751; https://doi.org/10.3390/cells9030751
Received: 21 February 2020 / Revised: 11 March 2020 / Accepted: 16 March 2020 / Published: 19 March 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Cutaneous Melanoma)
Ectopic expression of RUNX2 has been reported in several tumors. In melanoma cells, the RUNT domain of RUNX2 increases cell proliferation and migration. Due to the strong link between RUNX2 and skeletal development, we hypothesized that the RUNT domain may be involved in the modulation of mechanisms associated with melanoma bone metastasis. Therefore, we evaluated the expression of metastatic targets in wild type (WT) and RUNT KO melanoma cells by array and real-time PCR analyses. Western blot, ELISA, immunofluorescence, migration and invasion ability assays were also performed. Our findings showed that the expression levels of bone sialoprotein (BSP) and osteopontin (SPP1) genes, which are involved in malignancy-induced hypercalcemia, were reduced in RUNT KO cells. In addition, released PTHrP levels were lower in RUNT KO cells than in WT cells. The RUNT domain also contributes to increased osteotropism and bone invasion in melanoma cells. Importantly, we found that the ERK/p-ERK and AKT/p-AKT pathways are involved in RUNT-promoted bone metastases. On the basis of our findings, we concluded that the RUNX2 RUNT domain is involved in the mechanisms promoting bone metastasis of melanoma cells via complex interactions between multiple players involved in bone remodeling. View Full-Text
Keywords: RUNX2; RUNT domain; PTHrP; bone; metastasis RUNX2; RUNT domain; PTHrP; bone; metastasis
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Deiana, M.; Dalle Carbonare, L.; Serena, M.; Cheri, S.; Mutascio, S.; Gandini, A.; Innamorati, G.; Lorenzi, P.; Cumerlato, M.; Bertacco, J.; Antoniazzi, F.; Romanelli, M.G.; Mottes, M.; Zipeto, D.; Valenti, M.T. A Potential Role of RUNX2- RUNT Domain in Modulating the Expression of Genes Involved in Bone Metastases: An In Vitro Study with Melanoma Cells. Cells 2020, 9, 751.

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