β7 integrins contribute to intestinal tumor growth in mice

PLoS One. 2018 Sep 20;13(9):e0204181. doi: 10.1371/journal.pone.0204181. eCollection 2018.

Abstract

The gut homing receptor integrin α4β7 is essential for the migration of pro-inflammatory T cells into the gut mucosa. Since intestinal neoplasia has been associated with chronic inflammation, we investigated whether interfering with gut-homing affects intestinal tumorigenesis. Using chemically induced and spontaneous intestinal tumor models we showed that lack of β7 integrin significantly impairs tumor growth without affecting tumor frequencies, with a mild translatable effect on overall survival. This correlates with human data showing lower MAdCAM-1 expression and disease-free survival in colorectal cancer patients. Thus, paradoxically in contrast to extra-intestinal tumors, blocking migration of immune cells into the gut might have a positive therapeutic effect on intestinal neoplasia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Proliferation
  • Inflammation / pathology
  • Integrin beta Chains / metabolism*
  • Intestinal Neoplasms / metabolism*
  • Intestinal Neoplasms / pathology*
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Inbred C57BL
  • Survival Analysis
  • T-Lymphocytes / immunology
  • Tumor Burden

Substances

  • Integrin beta Chains
  • integrin beta7

Grants and funding

JRM was supported by grants from CCFA, Cancer Research Institute (CRI), and NIH DP2 2009A054301. SD was supported by Cancerfonden (CAN2016/1206), MQJ was supported by grants from the Swedish Research Council and the Swedish Cancer Foundation and EJV was supported by grants from Crohn’s & Colitis Foundation of America (CCFA), Swedish Research Council VR grant K2015-68X-22765-01-6, Formas grant nr. FR-2016/0005 and Wallenberg Academy Fellow (WAF) program (WAF2014). The funder did not play a role in any step associated to this study and only provided financial support in the form of authors' salaries and/or research materials. Moreover, Takeda Pharmaceuticals only provided support in the form of salaries for author JRM, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.