PTX3, the gene which is able to slow down cancer
This is the surprising achievement of the research study coordinated by Alberto Mantovani, Humanitas University Professor and Vice Rector for Research, and funded by AIRC – Italian Association for Cancer Research.
Published on the highly influential scientific journal Cell, the study reveals the existence of a gene which is able to “turn off” cancer by controlling the inflammation responsible for the birth and growth of the tumour, differently from all the other known oncosuppressors which act directly on the tumour cell.
“To understand the relevance of this study, involving many Humanitas doctors and researchers, in cooperation with eminent international institutes – explains Prof. Mantovani – we have to remember the characteristics of a tumour cell: its oncogenes (the genes responsible for its reproduction) are always active, while the oncosuppressors (blocking the tumour growth) are turned off, just like a car with accelerator pushed to the limits and broken brakes; furthermore, the tumour cell is part of a special ecologic niche, an inflammatory sub-environment in which and thanks to which the cell can grow and proliferate”.
For the first time, a study shows that an essential component of innate immunity, PTX3*, discovered 20 years ago by Prof. Mantovani and his team, acts as an oncosuppressor with a new and unique mechanism, i.e. it slows down the cancer development by controlling the inflammatory response. “Our researches have shown that in some tumours (colon, skin and a type of sarcomas) – Mantovani goes on – PTX3 is precociously turned off. The turning off removes the brakes blocking a cascade of mediators of the inflammation called ‘complement‘. In this way, the tumour can recruit ‘corrupt cops’, the macrophages, capable of promoting its growth. “
This unexpected discovery promises notable implications on the clinical ground and so it represents a reason to activate a further clinical experimentation of the PTX3 molecule (already on a trial as a drug against Aspergillus infections in patients with tumours) as an anticancer drug.
* PTX3 Is an Extrinsic Oncosuppressor Regulating Complement-Dependent Inflammation in Cancer
Eduardo Bonavita,1 Stefania Gentile,1 Marcello Rubino,1 Virginia Maina,1 Roberto Papait,1,2 Paolo Kunderfranco,1 Carolina Greco,1 Francesca Feruglio,1 Martina Molgora,1 Ilaria Laface,1 Silvia Tartari,1 Andrea Doni,1 Fabio Pasqualini,1 Elisa Barbati,1 Gianluca Basso,1 Maria Rosaria Galdiero,1 Manuela Nebuloni,3 Massimo Roncalli,1 Piergiuseppe Colombo,1 Luigi Laghi,1 John D. Lambris,4 Se´ bastien Jaillon,1 Cecilia Garlanda,1 and Alberto Mantovani1,5
1 Humanitas Clinical and Research Center, Rozzano (Milan) 20089, Italy
2 Institute of Genetics and Biomedical Research, National Research Council, Rozzano (Milan) 20089, Italy
3 Pathology Unit, L. Sacco Department of Clinical Sciences, University of Milan, Milan 20157, Italy
4 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5 Humanitas University, Rozzano (Milan) 20089, Italy