U.O. name

Endocrinology

Scientific Coordinator

Dott. Diego Ferone

Description

The Unit of Endocrinology has been studying the fisiopathology of somatostatin receptors (SSRs), dopamine receptors (DRs) and growth factor receptors in different cell lines and primary cultures from neuroendocrine and non-neuroendocrine tumors for several years. In particular, the Unit of Endocrinology focused its attention on the role of these receptors in pituitary adenomas, in neuroendocrine tumors (NET), in prostate cancer (PCa) and in lung cancer as prognostic markers in the combined therapy with first- and second-generation somatostatin analogues (SSAs) and dopamine-agonists (DAs). Moreover, since it has been clearly demonstrated that SSRs and DRs can dimerize on cell membrane (omo- and/or etero-dimerization) in several cell models, the Unit of Endocrinology has been studying this phenomenon as a consequence of the treatment, not only with the SSAs commonly used in clinical practice (octreotide and lanreotide), but also of the treatment with new SSAs such as panligands and bi-specific or chimeric compounds.
Furthermore, the Unit is involved in studies of cellular and molecular biology aimed to isolate and characterize cancer stem cells obtained from cerebral tumors such as glioblastomas and meningiomas in order to study their role as pharmacological target in these tumors.

List of pubblications

  1. Bacigaluppi S, Gatto F, Anania P, Bragazzi NL, Rossi DC, Benvegnu G, Nazzari E, Spaziante R, Giusti M, Ferone D, Zona G. Impact of pre-treatment with somatostatin analogs on surgical management of acromegalic patients referred to a single center. Endocrine. 2015 May 17. PMID: 25982150
  2. Cuny T, Barlier A, Feelders R, Weryha G, Hofland LJ, Ferone D, Gatto F. Medical therapies in pituitary adenomas: Current rationale for the use and future perspectives. Ann Endocrinol (Paris). 2015 Feb;76(1):43-58. PMID: 25556152
  3. Barbieri F, Thellung S, Würth R, Gatto F, Corsaro A, Villa V, Nizzari M, Albertelli M, Ferone D, Florio T. Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System. Int J Endocrinol. 2014;2014:753524. Review. PMID: 25484899
  4. Gatto F, Grasso LF, Nazzari E, Cuny T, Anania P, Di Somma C, Colao A, Zona G, Weryha G, Pivonello R, Ferone D. Clinical outcome and evidence of high rate post-surgical anterior hypopituitarism in a cohort of TSH-secreting adenoma patients: Might somatostatin analogs have a role as first-line therapy? Pituitary. 2015 Oct;18(5):583-91. PMID: 25326851
  5. Ruscica M, Magni P, Steffani L, Gatto F, Albertelli M, Rametta R, Valenti L, Ameri P, Magnaghi V, Culler MD, Minuto F, Ferone D, Arvigo M. Characterization and sub-cellular localization of SS1R, SS2R, and SS5R in human late-stage prostate cancer cells: effect of mono- and bi-specific somatostatin analogs on cell growth. Mol Cell Endocrinol. 2014 Feb 15;382(2):860-70. PMID: 24211300
  6. Gritti M., Würth R., Angelini M., Barbieri F., Peretti M., Pizzi E., Pattarozzi A., Carra E., Sirito R., Daga A., Curmi P., Mazzanti M. and Florio T. “Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current” Oncotarget 5: 11136-11152 (2014).
  7. Mohamed A., Blanchard M.P., Albertelli M., Barbieri F., Brue T., Niccoli P., Delpero J-R., Monges G., Garcia S., Ferone D., Florio T., Enjalbert A., Moutardier V., Schonbrunn A., Gerard C., Barlier A., Saveanu A. “Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pNETs cultures” Endocrine-Related Cancer 21: 691-704 (2014).
  8. Barbieri F., Albertelli M., Grillo F., Mohamed A. Saveanu A., Barlier A., Ferone D. and Florio T. “Neuroendocrine tumors: insights on innovative therapeutic options and rational development of targeted therapies” (REVIEW) Drug Discovery Today 19: 458-468 (2014).
  9. Gatto F, Feelders R, van der Pas R, Kros JM, Dogan F, van Koetsveld PM, van der Lelij AJ, Neggers SJ, Minuto F, de Herder W, Lamberts SW, Ferone D, Hofland LJ. β-Arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: role in the regulation of response to somatostatin analogue treatment in patients with acromegaly. Endocrinology. 2013 Dec;154(12):4715-25. PMID: 24169548
  10. Gatto F, Feelders RA, van der Pas R, Kros JM, Waaijers M, Sprij-Mooij D, Neggers SJ, van der Lelij AJ, Minuto F, Lamberts SW, de Herder WW, Ferone D, Hofland LJ. Immunoreactivity score using an anti-sst2A receptor monoclonal antibody strongly predicts the biochemical response to adjuvant treatment with somatostatin analogs in acromegaly. J Clin Endocrinol Metab. 2013 Jan;98(1):E66-71. PMID: 23118420
  11. Gatti M., Pattarozzi A., Bajetto A., Würth R., Daga A., Fiaschi P., Zona G., Florio T., Barbieri F. “Inhibition of CXCL12/CXCR4 autocrine/paracrine loop reduces viability of human glioblastoma stem-like cells affecting self-renewal activity” Toxicology 314: 209-220 (2013).
  12. Würth R., Pattarozzi A., Gatti M., Bajetto A., Corsaro A., Parodi A., Sirito R., Massollo M., Marini C., Zona G., Fenoglio D., Sambuceti G., Filaci G., Daga A., Barbieri F. and Florio T. “Metformin selectively affects human glioblastoma tumor-initiating cell viability: a role for metformin-induced inhibition of Akt” Cell Cycle 12: 145-156 (2013).
  13. Ferone D, Gatto F, Minuto F. Pre-surgical treatment with somatostatin analogues in patients with acromegaly: the case for. J Endocrinol Invest. 2012 Jun;35(6):613-5. PMID: 22776973
  14. Gatto F, Barbieri F, Gatti M, Wurth R, Schulz S, Ravetti JL, Zona G, Culler MD, Saveanu A, Giusti M, Minuto F, Hofland LJ, Ferone D, Florio T. Balance between somatostatin and D2 receptor expression drives TSH-secreting adenoma response to somatostatin analogues and dopastatins. Clin Endocrinol (Oxf). 2012 Mar;76(3):407-14. PMID: 21848909
  15. Ferone D, Pivonello R, Kwekkeboom DJ, Gatto F, Ameri P, Colao A, de Krijger RR, Minuto F, Lamberts SW, van Hagen PM, Hofland LJ. Immunohistochemical localization and quantitative expression of somatostatin receptors in normal human spleen and thymus: Implications for the in vivo visualization during somatostatin receptor scintigraphy. J Endocrinol Invest. 2012 May;35(5):528-34. PMID: 21765239
  16. Barbieri F., Wurth R., Ratto A., Campanella C., Vito G., Thellung S., Daga A., Cilli M., Ferrari A. and Florio T. “Isolation of stem-like cells from spontaneous feline mammary carcinomas: phenotypic characterization and tumorigenic potential” Experimental Cell Research 318: 847-860 (2012).
  17. Gatto F, Barbieri F, Castelletti L, Arvigo M, Pattarozzi A, Annunziata F, Saveanu A, Minuto F, Castellan L, Zona G, Florio T, Ferone D. In vivo and in vitro response to octreotide LAR in a TSH-secreting adenoma: characterization of somatostatin receptor expression and role of subtype 5. Pituitary. 2011 Jun;14(2):141-7. PMID: 21086053
  18. Arvigo M, Gatto F, Ruscica M, Ameri P, Dozio E, Albertelli M, Culler MD, Motta M, Minuto F, Magni P, Ferone D. Somatostatin and dopamine receptor interaction in prostate and lung cancer cell lines. J Endocrinol. 2010 Dec;207(3):309-17. doi: 10.1677/JOE-10-0342. Epub 2010 Sep 27. PMID: 20876239
  19. Boschetti M, Gatto F, Arvigo M, Esposito D, Rebora A, Talco M, Albertelli M, Nazzari E, Goglia U, Minuto F, Ferone D Role of dopamine receptors in normal and tumoral pituitary corticotropic cells and adrenal cells. Neuroendocrinology. 2010;92 Suppl 1:17-22. Review. PMID: 20829613
  20. Ruscica M, Arvigo M, Gatto F, Dozio E, Feltrin D, Culler MD, Minuto F, Motta M, Ferone D, Magni P. Regulation of prostate cancer cell proliferation by somatostatin receptor activation. Mol Cell Endocrinol. 2010 Feb 5;315(1-2):254-62. Erratum in: Mol Cell Endocrinol. 2011 Jul 20;341(1-2):89. PMID: 19932151

Main research lines

  • IGF system: studies on the role of IGF system (IGF / IGFBP / IGFBP proteases and IGF receptors) in the proliferation and differentiation of primary cultures and cell lines from different tumors (lung and prostate cancer, osteoblasts).
  • Somatostatin system: evaluation of SSR (SSTR1-5) and dopamine (D2R) profile in neoplastic tissues and in cell cultures obtained from endocrine and non-endocrine tumors; role of SSAs and SSTR-DR chimeric compounds on cell proliferation of tumor cell lines and primary cultures obtained from different tumors; evaluation of the interactions between IGF and somatostatin/SSRs system.
  • Cancer stem cells (CSC):isolation and characterization of cancer stem cells obtained from cerebral tumors such as glioblastomas and meningiomas; role of CSC as pharmacological target in these tumors.
  • Biology and pharmacology of prion disease: synthesis and purification of prion protein sequences; analysis of localization and toxicity of prion proteins. 

Settore ERC del gruppo

MED/13 Endocrinologia, BIO 14/Farmacologia

Componenti

Cognome Nome Dipartimento di afferenza Qualifica Settore
Ferone Diego DIMI Ricercatore Neuroendocrinologia
Boschetti Mara IMI Ricercatore Ipopituitarismo
Arvigo Marica DIMI Ricercatore TD Ricerca traslazionale
Florio Tullio DIMI Prof Associato Farmacologia
Barbieri Federica DIMI Ricercatore Farmacologia
Thellung De Courtelary Stefano DIMI Ricercatore TD Farmacologia

Collaborations

  • Erasmus Medical Center, University of Rotterdam, The Netherlands
  • University of Cordoba, University of Rome, University of Uppsala, University of Verona, University of Paris, University of Berlin (progetto IPSEN CONSORTIUM NET R-Hub)
  • Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Italy and Department of Endocrinology and Laboratory CRN2M (Centre de Recherche en Neurobiologie - Neurophysiologie de Marseille), University of Marseilles, France (progetto MAGNET)
  • University of Naples, University of Ferrara (progetto FIRB Progetto RBAP11884M_006)
  • Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy (PROGETTO SSRs e CARCINOMA PROSTATICO)

Fundings

  • PROSTATE CANCER
    • FIRB Project RBAP11884M_006 (PI: Prof. Diego Ferone) “Advanced technological platforms for the definition of new biomarkers and molecular targets in nano-technological vectors for diagnosis and therapy of human neoplasias”.
      Study Sponsor: MIUR, 2011
    • PROJECT SSRs AND PROSTAE CANCER (PI: Prof. Diego Ferone) “Somatostatin and prostate cancer: role of somatostatin receptors in the control of tumour growth”.
      Study Sponsor: IPSEN
  • PRION DISEASE
    • FIRB Project RBAP11HSZS_002 (PI: Prof. Tullio Florio) “Neurodegenerative pathologies and cerebral damage: cellular and molecular mechanisms resulting in cognitive impairment and correlation to the functional damage in humans” (2012-2016)
    • COMPAGNIA DI SAN PAOLO (PI: Prof. Tullio Florio) “Study of molecular determinants involved in prion protein conversion into its neurotoxic form to identify new pharmacological targets” (2014-2016)