Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Sci Rep. 2017 Nov 29;7(1):16567. doi: 10.1038/s41598-017-16738-y.

A novel role for OATP2A1/SLCO2A1 in a murine model of colon cancer.

Author information

1
Kanazawa University, Kanazawa, 920-1192, Japan. nakanish@p.kanazawa-u.ac.jp.
2
Kanazawa University, Kanazawa, 920-1192, Japan.
3
Faculty of Pharmacy, Kindai University, Higashiosaka, Osaka, Japan.
4
Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
5
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.

Abstract

Prostaglandin E2 (PGE2) is associated with proliferation and angiogenesis in colorectal tumours. The role of prostaglandin transporter OATP2A1/SLCO2A1 in colon cancer tumorogenesis is unknown. We evaluated mice of various Slco2a1 genotypes in a murine model of colon cancer, the adenomatous polyposis (APC) mutant (Apc ∆716/+) model. Median lifespan was significantly extended from 19 weeks in Slco2a1 +/+/Apc Δ716/+ mice to 25 weeks in Slco2a1 -/-/Apc Δ716/+ mice. Survival was directly related to a reduction in the number of large polyps in the Slco2a1 -/- /Apc ∆716/+ compared to the Slco2a1 +/+/Apc Δ716/+ or Slco2a1 +/-/Apc Δ716/+mice. The large polyps from the Slco2a1 -/- /Apc ∆716/+ mice had significant reductions in microvascular density, consistent with the high expression of Slco2a1 in the tumour-associated vascular endothelial cells. Chemical suppression of OATP2A1 function significantly reduced tube formation and wound-healing activity of PGE2 in human vascular endothelial cells (HUVECs) although the amount of extracellular PGE2 was not affected by an OATP2A1 inhibitor. Further an in vivo model of angiogenesis, showed a significant reduction of haemoglobin content (54.2%) in sponges implanted into Slco2a1 -/-, compared to wildtype mice. These studies indicate that OATP2A1 is likely to promote tumorogenesis by PGE2 uptake into the endothelial cells, suggesting that blockade of OATP2A1 is an additional pharmacologic strategy to improve colon cancer outcomes.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center