Environmental Enrichment Induces Pericyte and IgA-Dependent Wound Repair and Lifespan Extension in a Colon Tumor Model

Publication date: 25 April 2017
Source:Cell Reports, Volume 19, Issue 4
Author(s): Benjamin D. Bice, Megan R. Stephens, Stephanie J. Georges, Ashlee R. Venancio, Peter C. Bermant, Annika V. Warncke, Kajsa E. Affolter, Julio R. Hidalgo, Melinda L. Angus-Hill
Environmental enrichment (EE) replicates mind-body therapy by providing complex housing to laboratory animals to improve their activity levels, behavior, and social interactions. Using a Tcf4^Het/+Apc^Min/+-mediated model of colon tumorigenesis, we found that EE vastly improved the survival of tumor-bearing animals, with differential effect on tumor load in male compared to female animals. Analysis of Tcf4^Het/+Apc^Min/+ males showed drastically reduced expression of circulating inflammatory cytokines and induced nuclear hormone receptor (NHR) signaling, both of which are common in the wound repair process. Interestingly, EE provoked tumor wound repair resolution through revascularization, plasma cell recruitment and IgA secretion, replacement of glandular tumor structures with pericytes in a process reminiscent of scarring, and normalization of microbiota. These EE-dependent changes likely underlie the profound improvement in survival of colon-tumor-bearing Tcf4^Het/+Apc^Min/+ males. Our studies highlight the exciting promise of EE in the design of future therapeutic strategies for colon cancer patients.

Graphical abstract

Teaser

Tumors are characterized as wounds that do not heal. Bice et al. show the beneficial effects of environmental enrichment on tumorigenesis in a mouse model of colon cancer. The authors demonstrate that EE improves the lifespan of tumor-bearing animals through the restoration of a wound-repair-like response within the tumor.


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2peRVty
via IFTTT