ECE2024 Eposter Presentations Adrenal and Cardiovascular Endocrinology (155 abstracts)
Emerging role of IGF1R and IR expression and localisation in adrenocortical carcinomas (ACC)
Rosa Catalano 1 , Emma Nozza 1,2 , Emanuela Esposito 1,2 , Anna Maria Barbieri 1 , Giorgio Croci 3 , Barbara Altieri 4 , Anna Angelousi 5 , Michaela Luconi 6,7 , Hantel Constanze 8,9 , Sandra Sigala 10 , Laura-Sophie Landwehr 4 , Guido Di Dalmazi 11,12 , Elisa Cassinotti 13 , Ludovica Baldari 13 , Serena Palmieri 14 , Alessandra Mangone 14 , Emanuele Ferrante 14 , Cristina Ronchi 15,16 , Giovanna Mantovani 1,14 & Erika Peverelli 1,14
1University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy; 2University of Milan, PhD Program in Experimental Medicine, Milan, Italy; 3Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pathology Unit, Milan, Italy; 4University Hospital, University of Würzburg, Division of Endocrinology and Diabetes Department of Internal Medicine I, Würzburg, Germany; 5National and Kapodistrian University of Athens, 5First Department of Internal Medicine, Laikon General Hospital, Medical School, Athens, Greece; 6University of Florence, Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, Florence, Italy; 7AOU Careggi, Centro di Ricerca e Innovazione sulle Patologie Surrenaliche, Florence, Italy; 8University Hospital Zurich and University of Zurich, Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland; 9University Hospital Carl Gustav Carus Dresden, Medical Clinic and Policlinic III, Dresden, Germany; 10University of Brescia, Section of Pharmacology, Department of Molecular and Translational Medicine, Brescia, Italy; 11IRCCS Azienda Ospedaliero-Universitaria di Bologna, Division of Endocrinology and Diabetes Prevention and Care, Bologna, Italy; 12Alma Mater Studiorum University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna, Italy; 13Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Department of Surgery, Milan, Italy; 14Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Endocrinology Unit, Milan, Italy; 15University of Birmingham, Institute of Metabolism and System Research, Birmingham, United Kingdom; 16Birmingham Health Partners, Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham, United Kingdom
Adrenocortical carcinomas (ACC) overexpress the insulin-like growth factor 2 (IGF2) that drives a proliferative autocrine loop by binding both IGF1R and isoform A of insulin receptor (IRA). However, the contribution of these receptors in mediating ACC cell growth has been poorly investigated. The aim of this study was to investigate IGF1R and IR expression and localisation in ACC and adrenocortical adenomas (ACA) samples, and to test their involvement in mediating IGF2 tumorigenic effects in ACC cells. To this end, we used four available cell lines and ACC primary cultures. Immunohistochemistry analysis on a cohort of ACC (n=116) and ACA (n=17) revealed that IGF1R was expressed in 85.3% of ACC and in all ACA. No difference in mean percentage of IGF1R positive cells, but a higher IGF1R plasma membrane localisation was observed in ACC (47.5%) compared to ACA (17.6%) (P<0.05). In ACC, IGF1R plasma membrane localisation was associated with a higher Ki67 (P<0.01), Weiss score (P<0.001) and among Weiss criteria, with a higher mitotic rate, presence of atypical mitoses and venous invasion. Moreover, IGF1R plasma membrane localisation showed a 7.5-fold increased risk of having Ki67≥10 (P<0.01). IR protein expression was found in 45.65% of ACC and in all ACA (P<0.001). In ACC, IR immunopositivity was associated with higher ENSAT stage, Ki67, Weiss score and a major risk of having a Ki67≥10 (P<0.05). RT-qPCR revealed that the prevalent isoform of IR was IRA in ACC (n=8), but not in ACA (n=8) (P<0.05). In ACC cell lines double IGF1R+IR silencing reduced cell proliferation in JIL2266 (-44.95 (16.04)%, P<0.05), MUC-1 (-46.31 (13.58)%, P<0.001) and TVBF-7 (-42.12 (15.89)%, P<0.001), but not H295R. The single IGF1R or IR knockdown inhibited cell growth only in MUC-1 cells. In ACC primary cultures (n=3), expressing higher levels of IRA than IRB, cell proliferation was reduced after IR but not IGF1R knockdown (P <0.05). In conclusion, we demonstrated that IGF1R plasma membrane localisation is more frequent in ACC than in ACA and is associated with a worse tumour behaviour in ACC. We further found in ACC an association between immunopositivity to IR, whose prevalent isoform is IRA, with more aggressive features. We first demonstrated a role of IR in mediating cell growth in ACC cells. Overall, these data suggest that: 1) IGF1R plasma membrane localisation and IR expression could represent biomarkers of more aggressive tumours; 2) IR, and in particular the spliced isoform IRA, might constitute a novel ACC therapeutic target.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more