IBMS BoneKEy | BoneKEy Watch
The angiopoietin-like protein 2 may be a useful therapeutic target to prevent osteosarcoma metastasis
DOI:10.1038/bonekey.2014.28
Odagiri et al. investigated the role of angiopoietin-like protein 2 (ANGPTL2) in vitro, in mouse models and in patient samples to assess its impact on metastasis of cells from a primary osteosarcoma.
Osteosarcoma cells grown as xenografts in mice showed greater ANGPTL2 expression, because of enhanced demethylation of the promoter region, compared to the same cell line grown in culture. In fact, promoter methylation was inversely correlated with protein expression levels.
ANGPTL2 was shown to enhance metastasis to the lungs in a mouse xenograft model. Osteosarcoma cells were stimulated to invade lung tissue through a pathway involving an increase in matrix metalloproteinase-9 activity and activation of MAPK (the p38 mitogen-activated protein kinase). In patient samples where there had been lung metastases, the researchers detected low levels of expression of tolloid-like 1 (TLL1) protease, which breaks ANGPTL2 into inactive fragments.
Editor’s comment: One of the most salient findings in this work is the observation that the TLL1 protease, which cleaves ANGPTL2 into inactive fragments, is not abundant in human osteosarcoma specimens. This suggests that increasing the expression or activity of TLL1 may be a useful strategy to delay the likelihood of metastasis in osteosarcoma patients.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.