Mechanobiology of cancer progression
Duration: September 1st 2022 – August 31st, 2027- Funded by ERC-AdG-2021 – G.A. nr 101053122
Project abstract
Invasive cancers are a leading cause of death worldwide, with almost ten million deaths per year caused by resistance to antitumor treatments. In breast cancer, aggressiveness correlates with fibrotic stiffening of the tumour. There is an urgent need to understand how the fibrotic microenvironment evolves, to design better targeted cancer therapies. Fibrotic stiffening is caused by fibroblasts secretion of a matrix with mechanical properties that stabilise the tumour vascular network. However, the hierarchy and stability of the tumour vascular network are not reproducible in vitro. To advance the field, I will develop a revolutionary platform able to recapitulate tumour fibrosis by exploiting the vascularisation of a living organism.
To achieve my goal, I will use human breast cancer cells adhering to 3D polymeric micro scaffolds to create arrays of tumour micro environments. I will implant the arrays in vivo in the chorioallantoic membrane of an embryonated avian egg, to elicit a foreign-body fibrotic reaction. I will vary the micro scaffolds geometry to condition tumour infiltration by the host’s vessels and cells. I will exploit fluorescent spatial beacons incorporated in the micro scaffolds for multiphoton image correlation, to derive morphological and functional information of the regenerated fibrous matrix and vessels. I will predict mass transport of solutes and anticancer agents by computational modelling. To validate the platform, I will quantify in vivo the dose-dependent efficacy and cancer specificity of therapeutic agents whose success is known to depend on the fibrotic stage of tumours.
This project combines mechanobiology to bioengineering, biomechanics, oncology, genetics, microtechnology, intravital imaging, biophysics and pharmacology to understand the progression mechanisms of the most incurable cancers. It will also provide an ethical and standardizable testing platform to boost the clinical translation of new therapeutic products in oncology.
Press
Vita.it, January 20, 2024
Breaking Latest News, August 17, 2022 – BEACONSANDEGG
Internazionale, August 16, 2022 – BEACONSANDEGG
LombardiaLifeScience.com, July 12, 2022 – BEACONSANDEGG
Openinnovation.regione.lombardia.com, July 8, 2022 – BEACONSANDEGG
Sole24Ore, May 18, 2022 – BEACONSANDEGG
Meteoweb.eu, April 27, 2022 – BEACONSANDEGG
Askanews.it, April 27, 2022 – BEACONSANDEGG
Publications
2024
Conci C, Sironi L, Jacchetti E, Panzeri D, Inverso D, Martinez Vasquez R, Osellame R, Collini M, Cerullo G, Chirico G, Raimondi MT. In vivo label-free tissue histology through a microstructured imaging window. APL Bioeng. 8, 016102 (2024). https://doi.org/10.1063/5.0165411. Repository link: https://re.public.polimi.it/handle/11311/1258496
2023
Donnaloja F, Raimond MT, Messa L, Barzaghini B, Carnevali F, Colombo E, Mazza D, Martinelli C, Boeri L, Rey F, Cereda C, Osellame R, Cerullo G, Carelli S, Soncini M, Jacchetti E. 3D photopolymerized microstructured scaffolds influence nuclear deformation, nucleo/cytoskeletal protein organization, and gene regulation in mesenchymal stem cells. APL Bioeng. 1 September 2023; 7 (3): 036112. https://doi.org/10.1063/5.0153215 Repository link: https://hdl.handle.net/11311/1249577
Testa C, Oliveto S, Jacchetti E, Donnaloja F, Martinelli C, Pinoli P, Osellame R, Cerullo G, Ceri S, Biffo S and Raimondi MT (2023), Whole transcriptomic analysis of mesenchymal stem cells cultured in Nichoid micro-scaffolds. Front. Bioeng. Biotechnol. 10:945474. doi: 10.3389/fbioe.2022.945474. Repository link: https://hdl.handle.net/11311/1228347
Donnaloja F, Limonta E, Mancosu C, Morandi F, Boeri L, Albani D, Raimondi MT. Unravelling the mechanotransduction pathways in Alzheimer’s disease. J Biol Eng. 2023 Mar 28;17(1):22. doi: 10.1186/s13036-023-00336-w. PMID: 36978103; PMCID: PMC10045049. Repository link: https://hdl.handle.net/11311/1235086