The Overlooked Role of Fat in Prostate Cancer

Medical News: How Adipose Tissue Drives Cancer Progression
A groundbreaking review from researchers at the University of Nebraska Medical Center-USA has shed light on a crucial yet underexplored aspect of prostate cancer progression: the role of adipose tissue. The research underscores that the fat surrounding our organs, especially in obese individuals, could be a significant player in cancer growth, metastasis, and resistance to treatment.


The Overlooked Role of Fat in Prostate Cancer
Adipose tissue and cancer are in constant crosstalk with one another. Adiponectin secreted by adipose tissue inhibits mTOR and in turn blocks proliferation, while leptin activates the JAK-STAT pathway to promote proliferation. Adipose tissue undergoes lipolysis secreting fatty acids that activate PPAR-γ, initiating angiogenesis in tumor cells. Immune cells from adipose tissue secrete pro-tumor factors aiding the tumor in evading the immune system. Adipose tissue also secretes cytokines such as CXCL12 and CCL7 to induce prostate cancer cell migration. Prostate cancer also releases cytokines such as IL-1B, which activates COX-2 and PGE2. PGE2 then cycles back to the tumor to promote migration and invasion through the cAMP-PKA/PI3K/AKT pathway. MiRNA-130 and TNF-α from cancer cells promote the dedifferentiation of adipocytes into cancer-associated adipocytes (CAAs). CAAs undergo enhanced lipolysis, feeding the cancer cells fatty acids.

Prostate cancer is one of the most common cancers affecting men worldwide. Despite significant advances in treatments, it remains a leading cause of cancer-related mortality, especially when it becomes metastatic or resistant to therapies. This study introduces an essential dimension to the discussion: how obesity and the changes it induces in adipose tissue contribute to these challenges. The findings emphasize the urgent need to address obesity not just as a metabolic condition but as a factor directly influencing cancer biology.
 
Adipose Tissue: More Than a Storage Depot
Adipose tissue, commonly referred to as body fat, has traditionally been viewed as a storage site for energy. However, modern science has revealed that it is a metabolically active organ, influencing various bodily functions through the release of hormones, signaling molecules (adipokines), and inflammatory agents. In healthy individuals, adipose tissue plays a supportive role, maintaining energy balance and metabolic health.
 
In obesity, however, the dynamics of adipose tissue change significantly. Fat cells enlarge and become stressed, leading to chronic inflammation, oxidative stress, and the release of abnormal levels of adipokines. These changes disrupt normal metabolic processes and create a microenvironment that is highly conducive to cancer development and progression.
 
The Tumor Microenvironment and Its Interplay with Fat
This Medical News report emphasizes the critical interplay between adipose tissue and the tumor microenviro nment (TME) in prostate cancer. The TME is the ecosystem in which a tumor resides, including nearby blood vessels, immune cells, and structural tissues. Adipose tissue, especially in obese individuals, acts as an active contributor to the TME by:
 
-Fueling Cancer Cells: Enlarged fat cells release free fatty acids and lipids that cancer cells use as an energy source. This supports their rapid growth and ability to spread.
 
-Suppressing Immune Responses: Obesity-induced inflammation alters immune cell activity, allowing cancer cells to evade immune detection and destruction.
 
-Promoting Therapy Resistance: Adipose tissue releases signaling molecules that reduce the effectiveness of treatments like chemotherapy and radiation.
 
How Obesity Impacts Prostate Cancer Progression
Prostate cancer progression is marked by several critical steps, including local growth, invasion into surrounding tissues, and eventual metastasis to distant organs. Obesity accelerates these processes in multiple ways:
 
-Inflammation: Chronic inflammation in obese adipose tissue creates a pro-tumorigenic environment. This inflammation involves immune cells, such as macrophages and T-cells, which instead of attacking the tumor, contribute to its growth.
 
-Oxidative Stress: Elevated levels of reactive oxygen species (ROS) in obese individuals damage DNA, lipids, and proteins, fostering genetic mutations and cancer progression.
 
-Adipokines: Obesity alters the secretion of critical signaling molecules like leptin and adiponectin. While leptin promotes cancer cell growth and angiogenesis (the formation of new blood vessels), adiponectin typically suppresses cancer; its levels are reduced in obesity.
 
How Fat Impacts Treatment Outcomes
The study reveals troubling insights into how adipose tissue interferes with standard prostate cancer treatments, including:
 
-Androgen Deprivation Therapy (ADT): ADT is a common treatment aimed at reducing levels of androgens (male hormones) that fuel prostate cancer growth. However, this therapy often leads to increased fat mass, which exacerbates inflammation and metabolic dysregulation. Adipose tissue affected by ADT releases factors that may contribute to resistance, making the treatment less effective over time.
 
-Chemotherapy: Fat cells can sequester chemotherapeutic drugs, reducing their availability to target cancer cells. Moreover, adipose tissue in obese individuals often metabolizes these drugs, further diminishing their effectiveness.
 
-Radiation Therapy: Radiation can alter the composition of adipose tissue, leading to increased oxidative stress and changes in the secretion of fatty acids and adipokines. These changes may inadvertently protect cancer cells and promote their survival and recurrence.
 
Prostate Cancer and Metabolism: The Role of Fat as Fuel
Prostate cancer cells adapt to their environment by using the resources available to them. In the presence of abundant fat, these cells shift their metabolism to rely heavily on fatty acids for energy. Fat cells release free fatty acids that are taken up by cancer cells and used to drive their growth. This metabolic flexibility makes prostate cancer particularly aggressive in obese individuals, where fat resources are abundant.
 
Adipose tissue also influences the production of building blocks necessary for cell membranes, proteins, and nucleic acids. Obesity further amplifies this process by providing an excess of these resources, allowing cancer cells to proliferate more rapidly.
 
Therapeutic Implications: Addressing Fat to Combat Cancer
Given the profound impact of adipose tissue on prostate cancer, targeting these interactions offers new therapeutic opportunities. Potential strategies include:
 
-Reducing Inflammation: Anti-inflammatory treatments may help counteract the pro-tumor effects of obese adipose tissue.
 
-Modifying Adipokine Signaling: Therapies designed to restore the balance of adipokines could inhibit cancer progression.
 
-Blocking Fatty Acid Metabolism: Inhibiting the pathways that cancer cells use to metabolize fatty acids may reduce their energy supply and limit growth.
 
Conclusions
The role of adipose tissue in prostate cancer progression is a critical area of research that demands greater attention. As obesity rates continue to rise globally, understanding how fat contributes to cancer biology will be essential for improving treatment outcomes. This study highlights the need for an integrated approach that addresses not only the tumor itself but also the surrounding microenvironment shaped by adipose tissue.
 
The findings underscore the importance of maintaining a healthy weight as part of cancer prevention and treatment strategies. Addressing obesity and its associated metabolic changes could improve the effectiveness of existing therapies and reduce the risk of cancer recurrence.
 
The study findings were published in the peer-reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/25/22/12137
 
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