Fig. 1: ECM remodeling effects in the obese TME.

The obese TME is marked by a variety of changes to the ECM architecture and stromal components. Obesity induces alterations to the ECM that not only affect the structure of the tumor-stroma but also drive recruitment of new cell types, which further modify the TME. The cumulative effect of recruitment and remodeling leads to a TME that is fundamentally distinct from that of lean individuals. Structural changes to the TME include expansion and excessive deposition of basement membrane components (see 1), a highly fibrotic matrix that is characterized by thickened and randomly aligned collagen fibers (see 2), enhanced collagen crosslinking by lysyl oxidases, and an increase in total matrix stiffness (see 7). Obesity-induced changes to the local cell populations include an increase in adipocyte size (see 3), a heightened predisposition for CAF differentiation from ASCs (see 4), and recruitment of M2 macrophage subtypes to the TME and subsequent TAM formation (see 5 and 6). The resulting pressure from increased size and ECM deposition from these cell types further contributes to ECM stiffening, an impact that is recognized by force-sensing machinery within the cancer cell and promotes pro-tumorigenic signaling and eventual disease progression (see 8 and 9).