Cellular and Molecular Pharmacology

Macroarea: Pharmacology

ERC sectors: LS1_9 Molecular mechanisms of signalling processes; LS3_5 Cell signalling and signal transduction, exosome biology; LS3_9 Cell differentiation, formation of tissues and organs; LS3_13 Stem cells; LS4_12 Cancer

Supervisors: Mayra Paolillo (RU), Cinzia Boselli (RU)

Junior Staff: Angelica Matarrese (Borsista)

1. The research activity mainly deals with cell infiltration mechanisms in tumor spread and metastasis formation in high grade brain tumors and even in other metastatic cancers. The experimental model is mainly represented by cancer stem cells (CSC) obtained from human tumor specimen, subsequently purified and characterized in vitro, or by de-differentiation of differentiated cancer cell lines through induction of the epithelial to mesenchymal transition (EMT) process. A large part of the research activity is devoted to the role of integrin receptors in the CSC intravasation process and metastatic spread, especially with regard to the functional effects induced by pharmacological blocking of RGD-binding integrins in CSC. A recently started research project deals with the development of a dynamic flow, 3D cell culture system to mimic CSC adhesion to a target tissue, with special attention to ECM composition of the pre-metastatic niche and the role of extracellular vesicles.

2. In our lab we set up a dynamic and multi-compartmental system to simulate physiologic processes, like the digestion process. Different cell types, gastric stromal cells and intestinal cells, are grown under appropriate conditions, according to tissue structure and function, to mimic gastric and intestinal absorption and to study metabolic profiles of potentially toxic molecules.

3. Extracellular vesicles (EV) Isolation and characterization of the two main classes of EV (microvesicles MV and exosomes EX) released by cancer glioma stem cells and astrocyte in cell cultures. MVs are isolated by differential ultracentrifugation (dUC) and their size are assessed by dynamic light scattering (DLS) and nanotracking particles analysis (NTA). The morphology of MVs is investigated by scanning microscopy (SEM) and transmission microscopy (TEM) and the expression of specific MV and EX markers are assessed by western blot. Uptake of MVs in recipient cells are measured by labeling MVs with fluorogenic dyes and then quantified by imaging flow cytometry (IFC) using Amnis equipment in collaboration with prof. Comincini lab Department of Biology and Biotechnology, Pavia).

4. Prof. Boselli research project deals with the study of innovative formulations for the treatment of chronic skin lesions. The aim of the research line is to test the wound healing efficacy of innovative platforms for tissue regeneration developed by the Biopharmaceutics and Formulation Development Laboratory of DDS in a murine model. The formulations are challenged to study their capability to deliver innovative natural products and/or drugs with anti-inflammatory, anti-infective, antifungal and/or antioxidant activity to modulate and shorten chronic wounds recovery and to prevent wound infections.

• In Vitro Glioblastoma Models: A Journey into the Third Dimension. Paolillo M, Comincini S, Schinelli S. Cancers (Basel). 2021 May 18;13(10):2449. https://doi.org/10.3390/cancers13102449
• Stem-Like Cancer Cells in a Dynamic 3D Culture System: A Model to Study Metastatic Cell Adhesion and Anti-Cancer Drugs. Paolillo M, Colombo R, Serra M, Belvisi L, Papetti A, Ciusani E, Comincini S, Schinelli S. Cells. 2019 Nov 13;8(11):1434. https://doi.org/10.3390/cells8111434
• Extracellular Matrix Alterations in Metastatic Processes. Paolillo M, Schinelli S. Int J Mol Sci. 2019 Oct 7;20(19):4947. https://doi.org/10.3390/ijms20194947
• A new millifluidic-based gastrointestinal platform to evaluate the effect of simulated dietary methylglyoxal intakes. Colombo R , Paolillo M , Papetti A . Food Funct. 2019 Jul 17;10(7):4330-4338. https://doi.org/10.1039/C9FO00332K
• A dimeric bicyclic RGD ligand displays enhanced integrin binding affinity and strong biological effects on U-373 MG glioblastoma cells. Sacco G, Dal Corso A, Arosio D, Belvisi L, Paolillo M, Pignataro L, Gennari C. Org Biomol Chem. 2019 Oct 21;17(39):8913-8917. https://doi.org/10.1039/C9OB01811E
• An RGD small-molecule integrin antagonist induces detachment-mediated anoikis in glioma cancer stem cells. Paolillo M, Galiazzo MC, Daga A, Ciusani E, Serra M, Colombo L, Schinelli S. Int J Oncol. 2018 Dec;53(6):2683-2694. https://doi.org/10.3892/ijo.2018.4583
• Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Wei Z, Batagov AO, Schinelli S, Wang J, Wang Y, El Fatimy R, Rabinovsky R, Balaj L, Chen CC, Hochberg F, Carter B, Breakefield XO, Krichevsky AM. Nat Commun. 2017 Oct 26;8(1):1145. doi: 10.1038/s41467-017-01196-x.
• Chitosan/glycosaminoglycan scaffolds for skin reparation. Sandri G, Rossi S, Bonferoni MC, Miele D, Faccendini A, Del Favero E, Di Cola E, Icaro Cornaglia A, Boselli C, Luxbacher T, Malavasi L, Cantu' L, Ferrari F.Carbohydr Polym. 2019 Sep 15;220:219-227. https://doi.org/10.1016/j.carbpol.2019.05.069
• Essential oil-loaded lipid nanoparticles for wound healing. Saporito F, Sandri G, Bonferoni MC, Rossi S, Boselli C, Icaro Cornaglia A, Mannucci B, Grisoli P, Vigani B, Ferrari F.Int J Nanomedicine. 2017 Dec 27;13:175-186. https://doi.org/10.2147/IJN.S152529
• Maltodextrin-amino acids electrospun scaffolds cross-linked with Maillard-type reaction for skin tissue engineering. Ruggeri M, Bianchi E, Rossi S, Boselli C, Icaro Cornaglia A, Malavasi L, Carzino R, Suarato G, Sánchez-Espejo R, Athanassiou A, Viseras C, Ferrari F, Sandri G. Journal of Materials Science & Engineering C In Press. https://doi.org/10.1016/j.msec.2021.112593

National collaborations

• Istituto neurologico C. Besta, Milano
• Azienda Ospedaliera Universitaria San Martino - IST, Genova

International collaborations

• Dr Alexander IVANOV, Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States

Fondo di Ateneo per la ricerca

Evaluation of toxicity and cell viability by in vitro assays; evaluation of cell proliferation and anti proliferative activity of molecules. Evaluation of gastric and intestinal absorption under dynamic conditions.