The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma
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Caterina Chiappetta1, Chiara Puggioni1, Raffaella Carletti1, Vincenzo Petrozza1, Carlo Della Rocca1 and Claudio Di Cristofano1
1UOC of Pathology, Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, Latina, Italy
Carlo Della Rocca, email: [email protected]
Keywords: osteosarcoma; KMT2C; tumorigenesis; metastasis; nuclear-cytoplasmic trafficking
Received: May 09, 2018 Accepted: June 25, 2018 Published: July 17, 2018
Osteosarcoma is the most common paediatric primary non-hematopoietic bone tumor; the survival is related to the response to chemotherapy and development of metastases. KMT2C is a chromatin-modifying and remodelling protein and its expression has never been studied in osteosarcoma. The aim of this study was to understand the role of KMT2C in the osteosarcoma carcinogenesis and metastatic progression to identify a new molecular target and to provide new therapeutic approach.
We performed the immunohistochemical and gene expression analysis of KMT2C in 32 samples of patients with diagnosis of osteosarcoma with known clinic-pathological data and we analysed the expression of genes involved in the metastatic pathway in four osteosarcoma cell lines by blocking the KMT2C expression using siRNA.
We found a nuclear-cytoplamic trafficking of KMT2C and the cytoplasmic localization was higher than the nuclear localization (p < 0.0001). Moreover, the percentage of cells with cytoplasmic positivity increased from low grade primary tissue to metastatic tissues. The cytoplasmic localization of KMT2C could lead to a change in its function supporting osteosarcoma carcinogenesis and progression. Our hypothesis is that KMT2C could affect the enhancer activity of genes influencing the invasive properties and metastatic potential of osteosarcoma.
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