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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2024

Open Access 01-12-2024 | Research

EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening

Authors: Ambra Cappelletto, Edoardo Alfì, Nina Volf, Thi Van Anh Vu, Francesca Bortolotti, Giulio Ciucci, Simone Vodret, Marco Fantuz, Martina Perin, Andrea Colliva, Giacomo Rozzi, Matilde Rossi, Giulia Ruozi, Lorena Zentilin, Roman Vuerich, Daniele Borin, Romano Lapasin, Silvano Piazza, Mattia Chiesa, Daniela Lorizio, Luca Triboli, Sandeep Kumar, Gaia Morello, Claudio Tripodo, Maurizio Pinamonti, Giulia Maria Piperno, Federica Benvenuti, Alessandra Rustighi, Hanjoong Jo, Stefano Piccolo, Giannino Del Sal, Alessandro Carrer, Mauro Giacca, Serena Zacchigna

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2024

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Abstract

Background

New drugs to tackle the next pathway or mutation fueling cancer are constantly proposed, but 97% of them are doomed to fail in clinical trials, largely because they are identified by cellular or in silico screens that cannot predict their in vivo effect.

Methods

We screened an Adeno-Associated Vector secretome library (> 1000 clones) directly in vivo in a mouse model of cancer and validated the therapeutic effect of the first hit, EMID2, in both orthotopic and genetic models of lung and pancreatic cancer.

Results

EMID2 overexpression inhibited both tumor growth and metastatic dissemination, consistent with prolonged survival of patients with high levels of EMID2 expression in the most aggressive human cancers. Mechanistically, EMID2 inhibited TGFβ maturation and activation of cancer-associated fibroblasts, resulting in more elastic ECM and reduced levels of YAP in the nuclei of cancer cells.

Conclusion

This is the first in vivo screening, precisely designed to identify proteins able to interfere with cancer cell invasiveness. EMID2 was selected as the most potent protein, in line with the emerging relevance of the tumor extracellular matrix in controlling cancer cell invasiveness and dissemination, which kills most of cancer patients.
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Metadata
Title
EMID2 is a novel biotherapeutic for aggressive cancers identified by in vivo screening
Authors
Ambra Cappelletto
Edoardo Alfì
Nina Volf
Thi Van Anh Vu
Francesca Bortolotti
Giulio Ciucci
Simone Vodret
Marco Fantuz
Martina Perin
Andrea Colliva
Giacomo Rozzi
Matilde Rossi
Giulia Ruozi
Lorena Zentilin
Roman Vuerich
Daniele Borin
Romano Lapasin
Silvano Piazza
Mattia Chiesa
Daniela Lorizio
Luca Triboli
Sandeep Kumar
Gaia Morello
Claudio Tripodo
Maurizio Pinamonti
Giulia Maria Piperno
Federica Benvenuti
Alessandra Rustighi
Hanjoong Jo
Stefano Piccolo
Giannino Del Sal
Alessandro Carrer
Mauro Giacca
Serena Zacchigna
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2024
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-023-02942-4

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