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  • Author: G P Bulfamante x
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C Verdelli Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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L Avagliano Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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P Creo Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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V Guarnieri Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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A Scillitani Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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L Vicentini Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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G B Steffano Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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E Beretta Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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L Soldati Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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E Costa Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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A Spada Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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G P Bulfamante Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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S Corbetta Laboratory of Molecular Biology, Department of Human Pathology, Laboratory of Stem Cells for Tissue Engineering, Medical Genetics, Endocrinology Unit, Endocrine Surgery, Surgery Unit, Surgery Unit, Department of Health Sciences, Endocrinology and Diabetology Unit, Endocrinology and Diabetology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy

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Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) showed an abundant periacinar distribution of α-SMA+ cells in normal parathyroid glands (n=3). This pattern was progressively lost in parathyroid adenomas (PAds; n=6) where α-SMA+cells were found to surround new microvessels, as observed in foetal parathyroid glands (n=2). Moreover, in atypical adenomas (n=5) and carcinomas (n=4), α-SMA+ cells disappeared from the parenchyma and accumulated in the capsula and fibrous bands. At variance with normal glands, parathyroid tumours (n=37) expressed high levels of fibroblast-activation protein (FAP) transcripts, a marker of tumour-associated fibroblasts. We analysed the ability of PAd-derived cells to activate fibroblasts using human bone-marrow mesenchymal stem cells (hBM-MSCs). PAd-derived cells induced a significant increase in FAP and vascular endothelial growth factor A (VEGFA) mRNA levels in co-cultured hBM-MSCs. Furthermore, the role of the calcium-sensing receptor (CASR) and of the CXCL12/CXCR4 pathway in the PAd-induced activation of hBM-MSCs was investigated. Treatment of co-cultures of hBM-MSCs and PAd-derived cells with the CXCR4 inhibitor AMD3100 reduced the stimulated VEGFA levels, while CASR activation by the R568 agonist was ineffective. PAd-derived cells co-expressing parathyroid hormone (PTH)/CXCR4 and PTH/CXCL12 were identified by FACS, suggesting a paracrine/autocrine signalling. Finally, CXCR4 blockade by AMD3100 reduced PTH gene expression levels in PAd-derived cells. In conclusion, i) PAd-derived cells activated cells of mesenchymal origin; ii) PAd-associated fibroblasts were involved in tumuor neoangiogenesis and iii) CXCL12/CXCR4 pathway was expressed and active in PAd cells, likely contributing to parathyroid tumour neoangiogenesis and PTH synthesis modulation.

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