Obesity Impacts on Prostate Cancer Progression

Obesity has emerged as a significant modifier of prostate cancer behaviour, with excess adiposity linked to increased incidence of aggressive disease, local dissemination and a poorer response to therapy. The expanding adipose depots that surround the prostate gland, notably the periprostatic fat, act not only as energy stores but as active endocrine and paracrine organs. They secrete a spectrum of adipokines, chemokines and bioactive lipids that reshape the tumour microenvironment by promoting chronic inflammation, angiogenesis and stromal remodelling. Obesity-induced alterations in sex hormone balance, insulin sensitivity and inflammatory mediators further drive oncogenic signalling pathways within prostate epithelial cells. In addition, metabolic reprogramming of cancer cells towards glycolysis and enhanced survival under stress conditions has been observed in the context of obesity. Epigenetic changes in both tumour and stromal cells may perpetuate these effects across generations. Collectively, these processes converge to accelerate tumour cell migration beyond the prostatic capsule, support metastatic colonisation and reduce the efficacy of standard therapies, underscoring the global importance of integrating weight-management strategies into prostate cancer care.

Research from Nature Portfolio

Recent foundational work has demonstrated that adipocytes in the periprostatic depot secrete the chemokine CCL7, which diffuses into adjacent prostate tissue to engage the CCR3 receptor on tumour cells. In obese models, elevated CCL7 enhances directed cell migration, facilitating extraprostatic extension; pharmacological inhibition of the CCR3–CCL7 axis abolishes this movement, highlighting a promising target to restrict local spread. Parallel studies have shown that obesity drives mobilisation of adipose stromal cells (ASCs) from white fat through gradients of CXCL1 and CXCL8 acting on CXCR1/2 receptors. Recruited ASCs adopt a myofibroblast-like phenotype marked by αSMA expression and promote neovascularisation within the tumour mass. This ASC influx accelerates prostate tumour growth and increases vascular density, suggesting that disrupting chemokine-driven stromal recruitment may attenuate obesity-associated tumour progression.

Obesity Impacts on Prostate Cancer Progression publication trend

The graph below shows the total number of articles in obesity impacts on prostate cancer progression across all publications each year (not limited to Nature Index journals).

Technical terms

Adipokine: A bioactive protein secreted by adipose tissue that modulates inflammation, metabolism and cell signalling.

Chemokine: A small signalling protein that directs the migration of immune or stromal cells by binding to specific receptors.

Browning (of adipose tissue): A process by which white fat adopts features of brown fat, including increased mitochondrial content and thermogenic capacity.

Adipose stromal cell (ASC): A multipotent cell resident in fat depots that can differentiate into fibroblast-like cells and influence tumour stroma.

Extraprostatic extension: The invasion of prostate cancer cells beyond the prostate capsule into adjacent tissues.

References

1. Castration promotes the browning of the prostate tumor microenvironment. Cell Communication and Signaling (2023).
2. Decoding the Influence of Obesity on Prostate Cancer and Its Transgenerational Impact. Nutrients (2023).
3. Periprostatic adipose tissue (PPAT) supernatant from obese mice releases anticontractile substances and increases human prostate epithelial cell proliferation: the role of nitric oxide and adenosine. Frontiers in Pharmacology (2023).
4. Periprostatic adipocytes act as a driving force for prostate cancer progression in obesity. Nature Communications (2016).
5. CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment. Nature Communications (2016).