Projet HEPINIB (Horizon Europe, appel à projets 2021)
Action : Staff Exchanges
Panel : Life Sciences
Statut du projet : SIGNED

Cancer is a leading cause of mortality within the aging European population. Therapeutic targeting is hampered by the complexity of the disease, which includes not only molecular changes within the tumor cell itself, but also within its microenvironment. Tumor angiogenesis, tumor-stroma interactions, interactions with immune cells, with the extracellular matrix and cancer stem cell niches allow for malignant cell survival and promote metastasis, the leading cause for cancer-associated mortality. Proteins substituted with the heparin-related carbohydrate heparan sulfate (HS) are dysregulated in malignant diseases, and are known to modulate all of the aforementioned processes of tumor progression. Several functions of HS-PGs in tumor progression are modulated by the enzyme heparanase (HPSE), which is barely expressed in adults, but upregulated during tumor progression, inflammation and angiogenesis, thus constituting an excellent drug target. Indeed, HPSE, the sole HS degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis and inflammation. HPSE accomplishes this by degrading HS and thereby regulating the bioavailability of heparin-binding proteins, priming the tumor microenvironment and mediating tumor-host crosstalk. We predict that therapeutic targeting of HPSE to be superior to conventional approaches, as it does not only have the potential to synchronously targeting tumor progression and metastasis at multiple levels (metastasis, angiogenesis, inflammation & immunity), but it is also be expected to have a favourable side effects profile. HEPINIB will combine leading experts of HPSE-related cancer research with non-academic partners providing a panel of innovative technologies with the aims of providing a deeper understanding of HPSE function in tumor progression, of developing novel HPSE inhibitors and delivery systems, and of trans-sectoral and interdisciplinary training of young scientists.

Mots clés : heparanase, glycosaminoglycans, heparin, proteoglycans, heparan sulfate

Participants :
- Université d'Uppsala (Suède) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 32200.0 €
- Serend-ip gmbh (Allemagne) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 13800.0 €
- Conseil national de la recherche (Italie) — Partner, beneficiary, Recherche, subvention : 41400.0 €
- Université de Münster (Allemagne) — Coordinator, beneficiary, Enseignement supérieur ou secondaire, subvention : 55200.0 €
- Technion - Institut de technologie d'Israël (Israël) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 13800.0 €
- Centro alta tecnologia istituto diricerchechimiche e biochimiche gronzoni srl (Italie) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 32200.0 €
- Competence Centre on Health Technologies (Estonia) (Estonie) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 64400.0 €
- Uppsala therapeutics ab (Suède) — Partner, beneficiary, Organismes privés (hors enseignement), subvention : 13800.0 €
- École polytechnique de Milan (Italie) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 46000.0 €
- Université de Reims Champagne-Ardenne (France) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 73600.0 €
- Conseil national de la recherche scientifique et technique (Argentine) — Partner, associated partner, Recherche, subvention : 0.0 €
- Université rhénane Frédéric-Guillaume de Bonn (Allemagne) — Partner, beneficiary, Enseignement supérieur ou secondaire, subvention : 50600.0 €