Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, 33006 Oviedo, Spain.
Departamento de Morfología y Biología Celular, Universidad de Oviedo, 33006 Oviedo, Spain.
Int J Mol Sci. 2024 Feb 7;25(4):2024. doi: 10.3390/ijms25042024.
Interaction between extracellular matrix (ECM) components plays an important role in the regulation of cellular behavior and hence in tissue function. Consequently, characterization of new interactions within ECM opens the possibility of studying not only the functional but also the pathological consequences derived from those interactions. We have previously described the interaction between fibulin2 and ADAMTS-12 in vitro and the effects of that interaction using cellular models of cancer. Now, we generate a mouse deficient in both ECM components and evaluate functional consequences of their absence using different cancer and inflammation murine models. The main findings indicate that mice deficient in both fibulin2 and ADAMTS12 markedly increase the development of lung tumors following intraperitoneal urethane injections. Moreover, inflammatory phenotype is exacerbated in the lung after LPS treatment as can be inferred from the accumulation of active immune cells in lung parenchyma. Overall, our results suggest that protective effects in cancer or inflammation shown by fibulin2 and ADAMTS12 as interactive partners in vitro are also shown in a more realistic in vivo context.
细胞外基质 (ECM) 成分之间的相互作用对细胞行为的调节起着重要作用，进而对组织功能也起着重要作用。因此，对 ECM 内新的相互作用进行特征描述不仅有可能研究这些相互作用的功能后果，也有可能研究其病理后果。我们之前已经在体外描述了纤连蛋白 2 和 ADAMTS-12 之间的相互作用，以及利用癌症的细胞模型研究了这种相互作用的影响。现在，我们生成了同时缺乏这两种 ECM 成分的小鼠，并利用不同的癌症和炎症小鼠模型来评估它们缺失的功能后果。主要发现表明，同时缺乏纤连蛋白 2 和 ADAMTS12 的小鼠在腹腔内注射尿嘧啶后，肺部肿瘤的发展明显增加。此外，LPS 处理后肺部的炎症表型加剧，这可以从肺实质中活性免疫细胞的积累推断出来。总的来说，我们的结果表明，纤连蛋白 2 和 ADAMTS12 作为体外相互作用的伙伴在癌症或炎症中表现出的保护作用，在更真实的体内环境中也表现出来。
