Higher sensitivity of Adamts12-deficient mice to tumor growth and angiogenesis

By M. E. Hour, Ángela Moncada-Pazos, S. Blacher, A. Masset, S. Cal, S. Berndt, J. Detilleux, Lorin Host, A. Obaya, Catherine Maillard and 4 more. 2010

107 citations recorded by the source corpus.

ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in tissue remodeling and angiogenesis associated with physiological and pathological processes. To elucidate the in vivo functions of ADAMTS-12, we have generated a knockout mouse strain (Adamts12−/−) in which Adamts12 gene was deleted. The mutant mice had normal gestations and no apparent defects in growth, life span and fertility. By applying three different in vivo models of angiogenesis (malignant keratinocyte transplantation, Matrigel plug and aortic ring assays) to Adamts12−/− mice, we provide evidence for a protective effect of this host enzyme toward angiogenesis and cancer progression. In the absence of Adamts-12, both the angiogenic response and tumor invasion into host tissue were increased. Complementing results were obtained by using medium conditioned by cells overexpressing human ADAMTS-12, which inhibited vessel outgrowth in the aortic ring assay. This angioinhibitory effect of ADAMTS-12 was independent of its enzymatic activity as a mutated inactive form of the enzyme was similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay than the wild-type form. Altogether, our results show that ADAMTS-12 displays antiangiogenic properties and protect the host toward tumor progression.

Subfields: Cancer Research, Immunology and Allergy, Molecular Biology

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In Cancer Research

1. R. Khalil
2. S. Zhong
3. Hideaki Nagase
4. D. Edwards
5. Gillian Murphy

In Immunology and Allergy

1. S. Zhong
2. R. Khalil

In Molecular Biology

1. R. Khalil
2. Hideaki Nagase
3. D. Edwards
4. S. Zhong

Citations in the corpus

• A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “Similarly, ADAMTS-12 shows antiangiogenic effects independent of its enzymatic activity as a mutated inactive form of the enzyme is similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay when compared to the control wild-type form, and these ADAMTS-12 antiangiogenic pr”
• Metalloproteinase‐dependent and ‐independent processes contribute to inhibition of breast cancer cell migration, angiogenesis and liver metastasis by a disintegrin and metalloproteinase with thrombospondin motifs‐15 (2015, background): “45 Angiogenesis inhibition that is metalloproteinase-independent has also been seen for ADAMTS-2,(15) ADAMTS-4,(46) ADAMTS-5,(47) and ADAMTS12.(48) This type of action may be common to many of the ADAMTS and ADAMTS-like proteins and involve the TSR domains, since peptides (termed “Adamtsostatins”) b”
• The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family (2015, background): “Once again, versican heterozygosity exacerbated the phenotype seen with mice deficient in ADAMTS20 Table 1 ADAMTS genes: their chromosomal positions, major tissue expression locations, expression-inducing factors bstrates, and associations with pathologies Gene Location Expression Factors inducing o”