Adipocytes: impact on tumor growth and potential sites for therapeutic intervention.
The prevalence of obesity has increased dramatically in recent decades, reaching epidemic proportions. It is becoming clear that obesity is associated not only with type 2 diabetes mellitus and cardiovascular disease, but also with multiple types of cancer. Obesity is characterized by impaired adipose tissue function, leading to adipocyte hypertrophy, inflammation, hypoxia and induced angiogenesis, extracellular matrix remodeling and fibrosis as well as additional stress responses. While epidemiological data indicate that obesity is a well-established risk factor for certain malignancies, the molecular mechanisms underlying the link between obesity and cancer are still poorly understood. Recent data implicates systemic and paracrine factors secreted from adipose tissue during the obese state, promoting cancer development and progression. Here, we focus on the obesity-associated adipose tissue remodeling that may not only lead to metabolic complications, but also to a permissive pro-tumorigenic environment. Particular attention is given to the local pro-tumorigenic effects derived from adipocytes that present an important part of the tumor microenvironment of at least some cancers, in an attempt to describe the nature of the major players of the adipocyte-cancer cell crosstalk that dictates to a large extent tumor progression.
Touchstone Diabetes Center, Departments of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Simona
S
Hefetz-Sela
Philipp E
PE
Scherer
D017667:Adipocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D054392:Adipokines / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D015992:Body Mass Index; D002454:Cell Differentiation / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009765:Obesity / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology; D012306:Risk
D054392:Adipokines