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Heparanase inhibition as a multifunctional targeting approach in cancer

Descripción del proyecto

Una nueva diana molecular para el cáncer

El heparán sulfato (HS) es un hidrato de carbono de estructura variada que se adhiere a las proteínas presentes en la superficie celular y en la matriz extracelular. Nuevos indicios revelan que este proceso está desregulado en el cáncer y afecta a las interacciones de las células cancerosas con el microentorno tumoral y el sistema inmunitario, favoreciendo así la progresión del cáncer y la metástasis. El objetivo del equipo del proyecto HEPINIB, financiado por las Acciones Marie Skłodowska-Curie, es utilizar como diana farmacológica la enzima heparanasa que descompone el HS y contribuye a la remodelación de la matriz extracelular. La hipótesis de trabajo es que la heparanasa como diana terapéutica actuará a muchos niveles e impedirá la metástasis, la angiogénesis y la inflamación.

Objetivo

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.

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Coordinador

UNIVERSITAET MUENSTER
Aportación neta de la UEn
€ 55 200,00
Dirección
Schlossplatz 2
48149 Muenster
Alemania

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Región
Nordrhein-Westfalen Münster Münster, Kreisfreie Stadt
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Aportación de la UE
Sin datos

Participantes (10)

Socios (1)