Metastatic niche shaped by host factors influences disseminated cancer cell fate.
TL;DR
A framework in which metastasis is dynamically codetermined by tumor cell plasticity and host systemic state is described, contextualized by recent mechanistic insights into how lifestyle and physiological states rewire organ microenvironments to become either permissive or restrictive to metastatic colonization is described.
Abstract
Metastasis is responsible for the vast majority of cancer-related deaths, yet organ selectivity and the fate of disseminated cancer cells remain incompletely understood. While tumor-intrinsic programs have been extensively characterized, increasing evidence indicates that host-related extrinsic factors critically modulate the molecular and cellular landscape of metastatic niches. Aging, dietary habits, microbiome, physical activity, smoking, air pollution, and chronic stress may reshape systemic inflammation, immune surveillance, vascular permeability, stromal composition, extracellular matrix remodeling, and metabolic signaling in organs commonly targeted by metastasis, including bone, lung, liver, and brain. These host-dependent alterations influence disseminated cancer cell homing, extravasation, dormancy, and proliferative outgrowth by reprogramming tissue-resident and recruited cell populations, as well as niche-derived soluble and mechanical cues. In this review, we describe a framework in which metastasis is dynamically codetermined by tumor cell plasticity and host systemic state, contextualized by recent mechanistic insights into how lifestyle and physiological states rewire organ microenvironments to become either permissive or restrictive to metastatic colonization. Understanding these interactions may reveal actionable targets for metastasis prevention and highlight modifiable behaviors as biological determinants of organ susceptibility to metastatic disease.