ECE2017 Eposter Presentations: Adrenal and Neuroendocrine Tumours Adrenal medulla (21 abstracts)
Role of microenvironment on proliferation and migration of an SDHB silenced murine Pheochromocytoma cell line
Serena Martinelli 1 , Vanessa D’Antongiovanni 1 , Susan Richter 3, , Letizia Canu 1 , Tonino Ercolino 1 , Graeme Eisenhofer 3, , Karel Pacak 5 , Elena Rapizzi 2 & Massimo Mannelli 1
1Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; 2Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; 3Institute of Clinical Chemistry & Laboratory Medicine, Dresden, Germany; 4Department of Medicine III, Technische Universitat Dresden, Dresden, Germany; 5Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Paragangliomas are rare neuroendocrine tumors derived from neural crest cells: if localized in the adrenal medulla they are called Pheocromocytomas (Pheo).The 30–40% of Pheo are mutated in one of the susceptibility genes among which there are genes encoding for the four subunits of the succinate dehydrogenase (SDH). Germ line mutations of SDHB are metastatic in about 80% of the cases. Surgery is the current therapy, but in presence of metastasis there is no effective treatment.
Using shRNA, we stably silenced for SDHB a Pheo murine cell line (MTT). The proliferative growth of non-silenced cells (CN) was higher than that of the silenced ones (B-). However, in co-culture with fibroblasts, the proliferation of B-was higher than that of the CN cultivated in the same conditions.
When cultured in fetal-bovine-serum (FBS), B- cells tended to aggregate more than the CN. When FBS was not present, both the cells lines lost this characteristic. When cultured in conditioned medium from activated murine fibroblasts (CAF), the aggregating effect disappeared, the cells assumed a longer shape and started migrating.
To understand whether this change corresponds to an epithelial to mesenchimal transition (EMT), we are evaluating the EMT markers and the expression of metalloproteases either secreted in the medium or expressed on membranes. To understand if the cross talk between fibroblasts and tumor cells was due to a signal mediated by receptors, we evaluated the phosphorylation of mTOR, Akt and ERK in B- and CN cells without detecting any difference.
These preliminary data suggest that the microenvironment, here represented by fibroblasts, affects the behaviour of cancer cells and studies on this interaction are needed to identify new therapeutic targets in SDHB mutated tumors.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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