Integrin alpha9 emerges as a key therapeutic target to reduce metastasis in rhabdomyosarcoma and neuroblastoma

Abstract

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.