Our laboratory is mainly focused to study: (1) the expression and role of K+ channels, and in particular of hERG1 (Kv 11.1) channels, in pancreatic ductal adenocarcinoma (PDAC) cells; (2) the interaction of hERG1 channels with plasma membrane receptors, and in particular with adhesion receptors of the integrin family, in PDAC cells; (3) the modulation exerted by hERG1 channels on intracellular signalling pathways controlling cell proliferation and survival, as well as cell migration and invasiveness.
Our team is also involved in the development and study of in vivo PDAC mouse models, and in particular (1) orthtotopic xenograft models employing luciferase-transfected PDAC cells; (2) genetically modified mice, either (a) Pdx-1-Cre, LSL-KrasG12D/+, LSL-Trp53R175H/+ transgenic (KPC) mice, which develop cancerous and precancerous lesions in the pancreas, or (b) LSL-hERG1 transgenic mice to be crossed with different Cre-expressing mice to activate hERG1 over expression in selected tissues.
Further technical expertise concerns (1) the production of monoclonal antibodies and engineered antibodies against ion channel proteins and (2) the development of primary cultures from human PDAC surgical samples.
Gasparoli L, D'Amico M, Masselli M, Pillozzi S, Caves R, Khuwaileh R, Tiedke W, Mugridge K, Pratesi A, Mitcheson JS, Basso G, Becchetti A, Arcangeli A. The New Pyrimido-indole Compound CD-160130 Preferentially Inhibits the KV11.1B Isoform and Produces Antileukemic Effects Without Cardio-toxicity. Mol Pharmacol. 87: 183-196, 2015.
Crociani O, Lastraioli E, Boni L, Pillozzi S, Romoli MR, D’Amico M, Stefanini M, Crescioli S, Taddei A, Bencini L, Bernini M, Farsi M, Beghelli S, Scarpa A, Messerini L, Tomezzoli A, Vindigni C, Morgagni P, Saragoni L, Giommoni E, Gasperoni S, Di Costanzo F, Roviello F, De Manzoni G, Bechi P, Arcangeli A. hERG1 channels regulate VEGF-A secretion in human gastric cancer: clinicopathologial correlations and therapeutical implications. Clin Cancer Res 20: 1502-1516, 2014.
Arcangeli A, Crociani O, Bencini L. Interaction of tumour cells with their microenvironment: ion channels and cell adhesion molecules. A focus on pancreatic cancer. Philos Trans R Soc Lond B Biol Sci. 369:20130101, 2014.
Sette A, Spadavecchia J, Landoulsi J, Casale S, Haye B, Crociani O, Arcangeli A. Development of novel anti-Kv 11.1 antibody-conjugated PEG-TiO(2) nanoparticles for targeting pancreatic ductal adenocarcinoma cells. J Nanopart Res 15:2111-2118, 2013.
Crociani O, Zanieri F, Pillozzi S, Lastraioli E, Stefanini M, Fiore A, Fortunato A, D'Amico M, Masselli M, De Lorenzo E, Gasparoli L, Chiu M, Bussolati O, Becchetti A, Arcangeli A. hERG1 channels modulate integrin signaling to trigger angiogenesis and tumor progression in colorectal cancer. Sci Rep. 3:3308-3329, 2013.
Fiore A, Carraresi L, Morabito A, Polvani S, Fortunato A, Lastraioli E, Femia AP, De Lorenzo E, Caderni G, Arcangeli A. Characterization of hERG1 channel role in mouse colorectal carcinogenesis. Cancer Med 2: 583-594, 2013.