Laboratory of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Pediatric Surgery Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Cell Mol Life Sci. 2022 Oct 11;79(11):546. doi: 10.1007/s00018-022-04557-y.
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.
目前大多数癌症疗法旨在抑制肿瘤生长，但缺乏可行的药理学方法来减少转移的形成。这是一个悖论，因为超过 90%的癌症死亡是由于转移进展。整合素 alpha9（ITGA9）先前被描述为在转移中发挥重要作用；然而，关于将这种蛋白质与该过程联系起来的机制知之甚少，它是研究较少的整合素之一。我们现在已经揭示了 ITGA9 在转移中的重要性，并提供了证据证明它在横纹肌肉瘤和神经母细胞瘤的转移扩散中是必不可少的。然而，这项研究最具转化意义的进展是首次揭示了通过用模拟 ADAM 蛋白关键相互作用域的合成肽抑制 ITGA9 来减少转移的可能性，在实验性转移模型中，不仅在儿童癌症中，而且在乳腺癌模型中也是如此。
