IRCCS Humanitas Research Hospital & Humanitas University
Published February 23, 2021 | Version v1
Dataset Restricted

Dataset related to article "Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer"

Authors/Creators

  • 1. IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy.
  • 2. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, Pieve Emanuele, Italy
  • 3. Department of Pathology, Humanitas Clinical, and Research Center-IRCCS, Milan, Italy.
  • 4. IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
  • 5. Area of Pathology, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy.
  • 6. Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy.
  • 7. Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy
  • 8. Laboratory of Molecular Gastroenterology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy
  • 9. Flow Cytometry Core, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
  • 10. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, Pieve Emanuele, Italy AND Colon and Rectal Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy.
  • 11. Department of Pathology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
  • 12. Department of Immunology and Inflammation, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy
  • 13. Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), Rionero in Vulture, Italy
  • 14. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, Pieve Emanuele, Italy AND IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy
  • 15. Department of Medicine and Surgery, University of Parma, Parma, Italy
  • 16. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, Pieve Emanuele, Italy AND Laboratory of Molecular Gastroenterology, Department of Gastroenterology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy

Description

This record contains raw data related to article “Unveiling role of sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer"

Background: Sphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.

Methods: We screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2-/-) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2-/-Lgr5-EGFP- mice.

Results: S1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/minmouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2-/- mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.

Conclusions: In normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.

Files

Restricted

The record is publicly accessible, but files are restricted. <a href="https://zenodo.org/account/settings/login?next=https://zenodo.org/records/4560431">Log in</a> to check if you have access.

Request access

If you would like to request access to these files, please fill out the form below.

You need to satisfy these conditions in order for this request to be accepted:

this set of data is accessible only upon request because it includes sensitive data.

please write your request to biblioteca@humanitas.it

You are currently not logged in. Do you have an account? Log in here

Additional details

Related works

Is supplement to
10.1186/s13046-020-01740-6 (DOI)
33225975 (ean8)