We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Ambrisentan, an endothelin receptor type A-selective antagonist, inhibits cancer cell migration, invasion, and metastasis.
- Authors
Kappes, Lucy; Amer, Ruba L.; Sommerlatte, Sabine; Bashir, Ghada; Plattfaut, Corinna; Gieseler, Frank; Gemoll, Timo; Busch, Hauke; Altahrawi, Abeer; Al-Sbiei, Ashraf; Haneefa, Shoja M.; Arafat, Kholoud; Schimke, Lena F.; Khawanky, Nadia El; Schulze-Forster, Kai; Heidecke, Harald; Kerstein-Staehle, Anja; Marschner, Gabriele; Pitann, Silke; Ochs, Hans D.
- Abstract
Several studies reported a central role of the endothelin type A receptor (ETAR) in tumor progression leading to the formation of metastasis. Here, we investigated the in vitro and in vivo anti-tumor effects of the FDA-approved ETAR antagonist, Ambrisentan, which is currently used to treat patients with pulmonary arterial hypertension. In vitro, Ambrisentan inhibited both spontaneous and induced migration/invasion capacity of different tumor cells (COLO-357 metastatic pancreatic adenocarcinoma, OvCar3 ovarian carcinoma, MDA-MB-231 breast adenocarcinoma, and HL-60 promyelocytic leukemia). Whole transcriptome analysis using RNAseq indicated Ambrisentan's inhibitory effects on the whole transcriptome of resting and PAR2-activated COLO-357 cells, which tended to normalize to an unstimulated profile. Finally, in a pre-clinical murine model of metastatic breast cancer, treatment with Ambrisentan was effective in decreasing metastasis into the lungs and liver. Importantly, this was associated with a significant enhancement in animal survival. Taken together, our work suggests a new therapeutic application for Ambrisentan in the treatment of cancer metastasis.
- Subjects
ENDOTHELINS; CANCER invasiveness; METASTASIS; PULMONARY artery diseases; PULMONARY hypertension
- Publication
Scientific Reports, 2020, Vol 10, Issue 1, pN.PAG
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-020-72960-1