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oai:recercat.cat:11351/86882025-11-26T05:33:18Zcom_2072_378071com_2072_378040col_2072_378097

Integrin alpha9 emerges as a key therapeutic target to reduce metastasis in rhabdomyosarcoma and neuroblastoma Molist Muñoz, Carla Zarzosa Martinez, Patricia Gallo, Gabriel Osvaldo Pons Barcons, Guillem Magdaleno Cazon, Ainara Hladun Alvaro, Raquel Segura Ginard, Miguel Sánchez de Toledo Codina, Josep Moreno Martín-Retortillo, Lucas Gallego Melcón, Soledad Roma Castanyer, Josep Navarro Barea, Natalia Sansa Girona, Júlia Guillén Burrieza, Gabriela Garrido Pontnou, Marta Tumors de parts toves - Tractament Sarcoma - Tractament Retina - Càncer - Tractament Metàstasi DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Muscle Tissue::Myosarcoma::Rhabdomyosarcoma DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Retinoblastoma DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Integrins Other subheadings::Other subheadings::/therapeutic use ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido muscular::miosarcoma::rabdomiosarcoma ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::retinoblastoma ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos::integrinas Otros calificadores::Otros calificadores::/uso terapéutico Dissemination; Paediatric cancer; Solid tumours Diseminación; Cáncer pediátrico; Tumores sólidos Disseminació; Càncer pediàtric; Tumors sòlids The majority of current cancer therapies are aimed at reducing tumour growth, but there is lack of viable pharmacological options to reduce the formation of metastasis. This is a paradox, since more than 90% of cancer deaths are attributable to metastatic progression. Integrin alpha9 (ITGA9) has been previously described as playing an essential role in metastasis; however, little is known about the mechanism that links this protein to this process, being one of the less studied integrins. We have now deciphered the importance of ITGA9 in metastasis and provide evidence demonstrating its essentiality for metastatic dissemination in rhabdomyosarcoma and neuroblastoma. However, the most translational advance of this study is to reveal, for the first time, the possibility of reducing metastasis by pharmacological inhibition of ITGA9 with a synthetic peptide simulating a key interaction domain of ADAM proteins, in experimental metastasis models, not only in childhood cancers but also in a breast cancer model. This research was supported by grants from: Institut Català d’Oncologia (ICO); Instituto de Salud Carlos III (PI18/00398 and FI18/00178); ACCIÓ (COMRDI15-1-0014); Fundació la Marató de TV3; Fundació A. BOSCH; Rotary Clubs Barcelona Eixample, Barcelona Diagonal, Santa Coloma de Gramanet, München-Blutenburg, Deutschland Gemeindienst e.V. and others from Barcelona and province; Eric Abidal Foundation; Del Hospital a la catedral Initiative by Xavi Vallès; and Mi compañero de viaje Association. 2022-12-19T13:07:46Z 2022-12-19T13:07:46Z 2022-10-11 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Cellular and Molecular Life Sciences;79 https://doi.org/10.1007/s00018-022-04557-y Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Springer Scientia