Comparative Approach to the Temporo-Spatial Organization of the Tumor Microenvironment.

Kendall L Langsten,Aaron L Sarver,Jong Hyuk Kim,Mark Dewhirst,Jaime F Modiano

doi:10.3389/fonc.2019.01185

Abstract

The complex ecosystem in which tumor cells reside and interact, termed the tumor microenvironment (TME), encompasses all cells and components associated with a neoplasm that are not transformed cells. Interactions between tumor cells and the TME are complex and fluid, with each facet coercing the other, largely, into promoting tumor progression. While the TME in humans is relatively well-described, a compilation and comparison of the TME in our canine counterparts has not yet been described. As is the case in humans, dog tumors exhibit greater heterogeneity than what is appreciated in laboratory animal models, although the current level of knowledge on similarities and differences in the TME between dogs and humans, and the practical implications of that information, require further investigation. This review summarizes some of the complexities of the human and mouse TME and interjects with what is known in the dog, relaying the information in the context of the temporo-spatial organization of the TME. To the authors' knowledge, the development of the TME over space and time has not been widely discussed, and a comprehensive review of the canine TME has not been done. The specific topics covered in this review include cellular invasion and interactions within the TME, metabolic derangements in the TME and vascular invasion, and the involvement of the TME in tumor spread and metastasis.

Highlights

Cancer, the uncontrolled proliferation of cells, is a significant cause of morbidity and mortality in humans and their canine companions worldwide [1, 2]
This review summarizes some of the complexities of the human and mouse tumor microenvironment (TME) and interjects with what is known in the dog, relaying the information in the context of the temporo-spatial organization of the TME
This review provides an overview of the complexity observed in the human and mouse TME, interjects known similarities and differences in the dog, and relays them in the context of the temporo-spatial organization of the TME

Summary

Introduction

The uncontrolled proliferation of cells, is a significant cause of morbidity and mortality in humans and their canine companions worldwide [1, 2]. Cell lines derived from these three tumor types were cultured under non-adherent low serum conditions that promote sphere formation and enrich CSCs. The steady state gene expression associated with CSC maintenance in tumors with high sphere-forming efficiency (i.e., hierarchically organized with relatively few CSCs) showed metabolic skewing toward fatty acid synthesis and secretion of immunosuppressive cytokines.

Results

Conclusion