Research

Generation of pancreatic tumor organoids

Research Topic

Patients diagnosed with locally advanced or metastatic pancreatic cancer have a five- year survival rate of less than 3%. Late presentation and high mortality highlight a need for early detection methods and new treatment strategies. More than 95% of pancreatic cancers originate from the exocrine compartment, comprised of acinar and ductal cells. The cellular origins of human pancreatic ductal adenocarcinoma (PDAC) are poorly understood. There are few in vitro models of exocrine pancreas development and primary human pancreatic adenocarcinoma (PDAC). Traditional models in oncology routinely relies on two-dimensional (2D) cell models, which inadequately recapitulate the physiologic context of cancer. Three-dimensional (3D) cell models are thought to better mimic the complexity of in vivo tumors. Several methods to culture 3D organoids have been described, but most are nonhomogeneous and expensive. In particular, only few studies have evaluated the efficacy and feasibility of organoids generation in pancreatic cancer. In this study we investigate  a new method that enables the production of organoids from tissue samples obtained from patients affected by pancreatic adenocarcinoma.


Research activities

The present study has the aim of obtaining in vitro organoids from tissue samples derived from patients affected by pancreatic adenocarcinoma. The technique developed by prof Stefano Piccolo research group was applied (Department of Molecular medicine, University of Padua). As case control, whenever possible, we have obtained also tissue sample from healthy pancreatic tissue as well. In addition to verify the feasibility and the success rate of these in vitro models, the study has the aim of investigate their capability to recapitulate ex vivo the molecular characteristics and the sensitivity to antitumour drugs. The creation of a bank  of in vitro organoids, especially from chemo resistant tumors, could represent a fundamental research tool in the setting of pancreatic cancer.


Ongoing Studies

a) evaluation of feasibility of generation of pancreatic tumor organoids from both neoplastic and healthy tissue in patients affected by pancreatic adenocarcinoma;
b) creation of an in vitro bank of pancreatic organoids and sampling  of DNA, RNA and ChIP seq.


5 selected publications

1) Marco Segatto, Raffaella Fittipaldi, Fabrizio Pin, Roberta Sartori, Kyung Dae Ko, Hossein Zare, Claudio Fenizia, Gianpietro Zanchettin, Elisa Sefora Pierobon, Shinji Hatakeyama, Cosimo Sperti, Stefano Merigliano, Marco Sandri,  Panagis Filippakopoulos, Paola Costelli, Vittorio Sartorelli, Giuseppina Caretti. Epigenetic Targeting of Bromodomain Protein BRD4 Counteracts Cancer Cachexia and Prolongs Survival. Nature Communications 2017; 8(1):1707

2) Mohelnikova-Duchonova B, Strouhal O, Hughes DJ, Holcatova I, Oliverius M, Kala Z, Campa D, Rizzato C, Canzian F, Pezzilli R, Talar-Wojnarowska R, Malecka-Panas E, Sperti C, Federico Zambon C, Pedrazzoli S, Fogar P, Milanetto AC, Capurso G, Delle Fave G, Valente R, Gazouli M, Malleo G, Teresa Lawlor R, Strobel O, Hackert T, Giese N, Vodicka P, Vodickova L, Landi S, Tavano F, Gioffreda D, Piepoli A, Pazienza V, Mambrini A, Pedata M, Cantore M, Bambi F, Ermini S, Funel N, Lemstrova R, Soucek P.  SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival. Sci Rep. 2017 Mar 8;7:43812

3) Sperti C, Gruppo M, Blandamura S, Valmasoni M, Pozza G, Passuello N, Beltrame V, Moletta L. Para-aortic node involvement is not an independent predictor of survival after resection for pancreatic cancer.World J  Gastroenterol. 2017 Jun 28;23(24):4399-4406

4) Rizzato C, Campa D, Talar-Wojnarowska R, Halloran C, Kupcinskas J, Butturini G, Mohelnikowa-Duchonova B, Sperti C, et al.  Association of genetic polymorphisms with survival of pancreatic ductal adenocarcinoma patients. Carcinogenesis 37,  957–964 (2016)

5) Basso D, Fogar P, Falconi M, Fadi E, SPERTI  C, Frasson C, Greco E, Tamburrino D, Teolato S, Moz S, Bozzato D, Pelloso M, Padoan A, De Franchis G, Gnatta E, Facco M, Zambon CF, Navaglia F, Pasquali C, Basso G, Semenzato G, Pedrazzoli S, Pederzoli P, Plebani M. Pancreatic tumors and immature immunosuppressive myeloid cells in blood and spleen: role of inhibitory co-stimulatory molecules PDL1 and CTLA4. An in vivo and in vitro study. PLoS One. 2013;8(1):e54824.

 

People involved:

Prof. Cosimo Sperti, Asociate Professor
Prof. Stefano Piccolo, Full Professor
Prof. Stella Blandamura, Associate Professor
Prof. Daniela Basso, Associate Professor
Dr. Lucia Moletta, Research Fellow