American Association for Cancer Research
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Figure S1 from Integrin-αvβ3 is a Therapeutically Targetable Fundamental Factor in Medulloblastoma Tumorigenicity and Radioresistance

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journal contribution
posted on 2023-12-07, 14:20 authored by William Echavidre, Jérôme Durivault, Célia Gotorbe, Thays Blanchard, Marina Pagnuzzi, Valérie Vial, Florian Raes, Alexis Broisat, Rémy Villeneuve, Régis Amblard, Nicolas Garnier, Cécile Ortholan, Marc Faraggi, Benjamin Serrano, Vincent Picco, Christopher Montemagno

Measurement of integrin-αvβ3 expression in MDB-derived cell lines performed by FACS. DAOY- and HD-MB03-derived cells were seeded in 6-well dishes for 24h. After detachment with accutase, cells were collected and incubated with an anti-αvβ3 antibody (ab190147, Abcam®) followed by a goat anti-mouse secondary antibody coupled to AlexaFluorTM488. Data were analyzed per sample using a BD FACSMelodyTM cytometer. Data were analyzed using FlowJoTM software.


Governement of the principality of Monaco

Fondation Flavien




Medulloblastoma is one of the most prevalent solid tumors found in children, occurring in the brain's posterior fossa. The standard treatment protocol involves maximal resection surgery followed by craniospinal irradiation and chemotherapy. Despite a long-term survival rate of 70%, wide disparities among patients have been observed. The identification of pertinent targets for both initial and recurrent medulloblastoma cases is imperative. Both primary and recurrent medulloblastoma are marked by their aggressive infiltration into surrounding brain tissue, robust angiogenesis, and resistance to radiotherapy. While the significant role of integrin-αvβ3 in driving these characteristics has been extensively documented in glioblastoma, its impact in the context of medulloblastoma remains largely unexplored. Integrin-αvβ3 was found to be expressed in a subset of patients with medulloblastoma. We investigated the role of integrin-αvβ3 using medulloblastoma-derived cell lines with β3-subunit depletion or overexpression both in vitro and in vivo settings. By generating radioresistant medulloblastoma cell lines, we uncovered an increased integrin-αvβ3 expression, which correlated with increased susceptibility to pharmacologic integrin-αvβ3 inhibition with cilengitide, a competitive ligand mimetic. Finally, we conducted single-photon emission computed tomography (SPECT)/MRI studies on orthotopic models using a radiolabeled integrin-αvβ3 ligand (99mTc-RAFT-RGD). This innovative approach presents the potential for a novel predictive imaging technique in the realm of medulloblastoma. Altogether, our findings lay the foundation for employing SPECT/MRI to identify a specific subset of patients with medulloblastoma eligible for integrin-αvβ3–directed therapies. This breakthrough offers a pathway toward more targeted and effective interventions in the treatment of medulloblastoma. This study demonstrates integrin-αvβ3’s fundamental role in medulloblastoma tumorigenicity and radioresistance and the effect of its expression on cilengitide functional activity.