Contribution of Adipose Tissue to Development of Cancer

Abstract

Solid tumor growth and metastasis require the interaction of tumor cells with the surrounding tissue, leading to a view of tumors as tissue-level phenomena rather than exclusively cell-intrinsic anomalies. Due to the ubiquitous nature of adipose tissue, many types of solid tumors grow in proximate or direct contact with adipocytes and adipose-associated stromal and vascular components, such as fibroblasts and other connective tissue cells, stem and progenitor cells, endothelial cells, innate and adaptive immune cells, and extracellular signaling and matrix components. Excess adiposity in obesity both increases risk of cancer development and negatively influences prognosis in several cancer types, in part due to interaction with adipose tissue cell populations. Herein, we review the cellular and noncellular constituents of the adipose “organ,” and discuss the mechanisms by which these varied microenvironmental components contribute to tumor development, with special emphasis on obesity. Due to the prevalence of breast and prostate cancers in the United States, their close anatomical proximity to adipose tissue depots, and their complex epidemiologic associations with obesity, we particularly highlight research addressing the contribution of adipose tissue to the initiation and progression of these cancer types. Obesity dramatically modifies the adipose tissue microenvironment in numerous ways, including induction of fibrosis and angiogenesis, increased stem cell abundance, and expansion of proinflammatory immune cells. As many of these changes also resemble shifts observed within the tumor microenvironment, proximity to adipose tissue may present a hospitable environment to developing tumors, providing a critical link between adiposity and tumorigenesis.

Visceral adipose tissue volume and CT‐attenuation as prognostic factors in patients with head and neck cancer

“…Dysfunctional adipocyte can secrete pro‐inflammatory cytokines and chemokines, which leads to inflammatory and fibrotic changes of adipose tissue . This alteration of adipose tissue is known to promote cancer cell growth and progression . Furthermore, cancer cells can inversely affect adipocytes by dedifferentiating adipocytes into fibroblast‐like cells, which increase the secretion of pro‐inflammatory cytokines and induce tumor cells to acquire more aggressiveness .…”

“…25 This alteration of adipose tissue is known to promote cancer cell growth and progression. 1,25,26 Furthermore, cancer cells can inversely affect adipocytes by dedifferentiating adipocytes into fibroblastlike cells, which increase the secretion of pro-inflammatory cytokines and induce tumor cells to acquire more aggressiveness. 1,25 In a previous study on nonhuman primates, increased attenuation of adipose tissue on noncontrast CT images corresponded to the inflammatory and fibrotic changes in adipose tissue, suggesting that the CT-attenuation of adipose tissue can be used as an indicator of the qualitative changes of adipose tissue.…”

Obesity and CD8 T cell metabolism: Implications for anti‐tumor immunity and cancer immunotherapy outcomes

“…A developing area of research within the broader field of cancer immunology is to determine whether obesity has a net positive or negative impact on specific facets of anti-tumor immunity, then discern the mechanisms by which obesity either diminishes or promotes protective anti-tumor mechanisms and tumor-promoting/ immunosuppressive factors. [120][121][122] We have found that in a preclinical model of orthotopic renal cancer, obesity is associated with an increased accumulation of regulatory dendritic cells within tumors. 123 When sort-purified, these CD11b+ dendritic cells were unable to activate naive CD8 T cells and induce their proliferation.…”

Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability

“…An important factor associated with obesity‐induced metabolic dysregulation is alterations in the adipose tissue . Adipose tissue is a dynamic endocrine organ, which apart from serving as an energy reservoir, has biochemical and metabolic functions that are implicated in cancer incidence and progression . Many groups have found that p53 levels are elevated in adipose tissue under conditions of chronic nutrient abundance.…”

“…19 Adipose tissue is a dynamic endocrine organ, which apart from serving as an energy reservoir, has biochemical and metabolic functions that are implicated in cancer incidence and progression. 20,21 Many groups have found that p53 levels are elevated in adipose tissue under conditions of chronic nutrient abundance. Contrary to its role as a tumor suppressor, the sustained activation of p53 signaling has been linked to the development of insulin resistance and adiposity.…”