Environmental Enrichment Induces Pericyte and IgA-Dependent Wound Repair and Lifespan Extension in a Colon Tumor Model
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
Affiliations
Benjamin D. Bice
Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA
Megan R. Stephens
Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA
Stephanie J. Georges
Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA
Ashlee R. Venancio
Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA
Peter C. Bermant
Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA
Annika V. Warncke
Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA
Kajsa E. Affolter
Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA
Julio R. Hidalgo
Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA
Melinda L. Angus-Hill
Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84132, USA
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 Tcf4Het/+ ApcMin/+-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 Tcf4Het/+ ApcMin/+ 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 Tcf4Het/+ ApcMin/+ males. Our studies highlight the exciting promise of EE in the design of future therapeutic strategies for colon cancer patients.
