Omentum and bone marrow: how adipocyte-rich organs create tumour microenvironments conducive for metastatic progression

Abstract

A number of clinical studies have linked adiposity with increased cancer incidence, progression and metastasis, and adipose tissue is now being credited with both systemic and local effects on tumour development and survival. Adipocytes, a major component of benign adipose tissue, represent a significant source of lipids, cytokines and adipokines, and their presence in the tumour microenvironment substantially affects cellular trafficking, signalling and metabolism. Cancers that have a high predisposition to metastasize to the adipocyte-rich host organs are likely to be particularly affected by the presence of adipocytes. Although our understanding of how adipocytes influence tumour progression has grown significantly over the last several years, the mechanisms by which adipocytes regulate the metastatic niche are not well-understood. In this review, we focus on the omentum, a visceral white adipose tissue depot, and the bone, a depot for marrow adipose tissue, as two distinct adipocyte-rich organs that share common characteristic: they are both sites of significant metastatic growth. We highlight major differences in origin and function of each of these adipose depots and reveal potential common characteristics that make them environments that are attractive and conducive to secondary tumour growth. Special attention is given to how omental and marrow adipocytes modulate the tumour microenvironment by promoting angiogenesis, affecting immune cells and altering metabolism to support growth and survival of metastatic cancer cells.

Keywords: Adipose tissue; MAT; WAT; bone metastasis; omental metastasis.

Figure 1

A schematic of proposed mechanisms underlying involvement of white adipose tissue and marrow adipose tissue in metastatic colonization and progression in omentum and bone. Omentum and bone are adipocyte-rich organs. Adipocytes in either depot have the propensity to fuel tumour growth and survival within the metastatic niche. Both depots are major sources of polyunsaturated fatty acids, Wnt ligands, free fatty acids, cytokines IL-6 and IL-8, MCP-1, and vascular endothelial growth factor (VEGF), all of which are known contributors to tumorigenesis. The specific marrow adipose tissue-derived factors such as TNF-α, IL-β, CXCL1, and CXCL2 as well as white adipose tissue-derived CXCL12, CD105, and VEGFR3, have also all been linked to metastatic disease. Tumour cells within an adipocyte-rich microenvironment have the ability to modulate adipocyte function by stimulating lipolysis and affecting secretion of pro-tumorigenic, pro-angiogenic and immunomodulatory factors. The interaction between adipocytes and tumour cells within the metastatic niche promotes metastatic progression through metabolic reprogramming or adaptation, immunomodulation, angiogenesis, epithelial-to-mesenchymal transformation (EMT) and growth factor/survival pathway signalling.