Tumor cell-derived angiopoietin-like protein ANGPTL2 is a critical driver of metastasis
Menée in vitro et à l'aide de xénogreffes, cette étude montre le rôle joué par une protéine des cellules tumorales, ANGPTL2, dans le processus métastatique
Strategies to inhibit metastasis have been mainly unsuccessful in part due to insufficient mechanistic understanding. Here we report evidence of critical role for the angiopoietin-like protein ANGPTL2 in metastatic progression. In mice, Angptl2 has been implicated in inflammatory carcinogenesis but it has not been studied in human tumors. In lung cancer patients, elevated levels of ANGPTL2 expression in tumor cells within the primary tumor were associated with a reduction in the period of disease-free survival after surgical resection. Transcription factors NFATc, ATF2 and c-Jun upregulated in aggressive tumor cells promoted increased Angptl2 expression. Most notably, tumor-cell derived ANGPTL2 increased in vitro motility and invasion in an autocrine/paracrine manner, conferring an aggressive metastatic tumor phenotype. In xenograft mouse models, tumor-cell derived ANGPTL2 accelerated metastasis and shortened survival, whereas attenuating ANGPTL2 expression in tumor cells blunted metastasis and extended survival. Overall, our findings demonstrated that tumor-cell derived ANGPTL2 drives metastasis and provided an initial proof of concept for blockade of its action as a strategy to antagonize the metastatic process.