Researchers at the University of Liege have been studying the role of ADAMTS-12, an enzyme which seems to have multiple functions. Having demonstrated its protective effect against cancer and asthma, researchers have now also shown that ADAMTS-12 seems to be crucial in order to avoid an exaggerated inflammatory response. These advances have been made possible thanks to a collaboration between a Spanish laboratory, a team from GIGA and the GIGA transgenic platform.  

The history of ADAMTS-12, a proteolytic enzyme, and ULg began in the context of the European program “Microenvimet” (2008-2012) whose area of research is cancerology. “We were working on matrix metalloproteinases (MMPs) which are very close to the ADAMTS family (for a disintegrin and metalloproteinase domain with thombospondin)”, explains Professor Agnès Noël, co-director of the Laboratory of tumor and development biology (LBTD) and former coordinator of Microenvimet. “Among the nine partners to this European program was the laboratory of Professor Carlos Lopez-Otin of the University of Oviedo in Spain”. Professor Lopez-otin was behind the identification of ADAMTS-12 and wanted to create knock-out mice for the ADAMTS-12 gene, that is to say, transgenic mice which are deficient in this gene. “We combined our efforts with the team of Carlos Lopez-Otin and researchers at GIGA”, she explains. This is the context in which the first knock-out mice of the GIGA transgenic platform were created. Since then a lot of progress has been made thanks to these little rodents!

A protective effect against cancer and asthma

In 2010, a first publication resulting from the creation of these mice appeared in the journal Oncogene (1). The objective of this work was to study the involvement of ADAMTS-12 in the process of tumor angiogenesis and cancer progression. In the absence of the afore-mentioned metalloproteinase, researchers observed an increase in the angiogenic response and tumor invasion into the tissues of the transgenic rodents. The results of this research therefore suggest that ADAMTS-12 plays a protective role against tumor angiogenesis and the progression of cancers (see also the article Metastases: the preparations for the crime).

“From here we explored the role of this enzyme in other pathologies such as asthma”, continues Agnès Noël. Professor Didier Cataldo also used the knock-out mice model for ADAMTS-12 in order to test whether the enzyme plays a role in the expression of asthmatic pathology (see article A gene called ADAM). The results, which were published last September in the Journal of Immunology (2), reveal that here too, ADAMTS-12 seems to have a protective effect. Indeed, the mice which are deficient in the ADAMTS-12 gene show much higher bronchial reactivity than the wild mice that were exposed to the same allergens. Moreover, by analyzing the rodents’ lungs, the scientists noticed an important increase in the number of eosinophils, which are key cells with regard to allergic inflammation.

(1)  M El Hour, A Moncada-Pazos, S Blacher, A Masset, S Cal, S Berndt, J Detilleux, L Host, A J Obaya, C Maillard, J M Foidart, F Ectors, A Noel and C Lopez-Otin2. Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis. Oncogene (2010) 29, 3025–3032; doi:10.1038/onc.2010.49; published online 8 March 2010.

(2) Paulissen G, El Hour M, Rocks N, Guéders MM, Bureau F, Foidart JM, Lopez-Otin C, Noel A, Cataldo DD. Control of Allergen-Induced Inflammation and Hyperresponsiveness by the Metalloproteinase ADAMTS-12. J Immunol. 2012 Oct 15;189(8):4135-43. doi: 10.4049/jimmunol.1103739. Epub 2012 Sep 7.