Prostate cancer is a prevalent disease in men, with more than 191,930 new cases expected to be diagnosed and 33,330 deaths to occur in the United States in 2020.

Various factors, such as genetics, age, and lifestyle choices, contribute to the development of this cancer. However, chronic inflammation has been recognized as a critical factor in prostate cancer initiation and progression.

What is Chronic Inflammation?

Inflammation is a natural and protective response of the immune system to injury or infection. It helps the body to repair damaged tissues and fight off harmful invaders such as bacteria, viruses, and toxins.

However, when inflammation persists for a prolonged period, it becomes chronic and can lead to many health problems, including cancer.

Chronic inflammation is a low-grade and systemic response characterized by the presence of inflammatory cells, cytokines, and chemokines.

It occurs when the immune system fails to eliminate the initial trigger, and instead, it starts attacking the healthy tissues, causing DNA damage, oxidative stress, and alterations in the tissue microenvironment.

The Link Between Chronic Inflammation and Prostate Cancer

Prostate cancer is a multifactorial and heterogeneous disease. Many genetic, environmental, and lifestyle factors contribute to its development and progression.

However, chronic inflammation has emerged as a critical factor that can trigger and promote the growth and spread of prostate cancer cells.

Several studies have shown that patients with chronic prostatitis, a long-lasting prostate inflammation, have a higher risk of developing prostate cancer.

The inflammation in the prostate gland generates free radicals and reactive oxygen species that can cause DNA mutations and damage the prostate cells’ genetic material. The inflammatory cells also produce cytokines and growth factors that can activate the cancer cells’ survival and proliferation pathways.

Furthermore, chronic inflammation can alter the prostate tissue microenvironment, making it more hospitable for the cancer cells to grow.

The inflammatory cells and molecules can stimulate the formation of new blood vessels, promoting the cancer cells’ nutrient and oxygen supply. They can also promote the production of extracellular matrix molecules that can facilitate the cancer cells’ invasion and migration to other parts of the body.

The Mechanisms of Chronic Inflammation in Prostate Cancer

The complex interactions between the immune system, inflammation, and cancer in the prostate gland present multiple mechanisms by which chronic inflammation can promote prostate cancer growth and progression. Here are some of the critical mechanisms:.

1. DNA Damage and Mutations

Chronic inflammation can generate free radicals and reactive oxygen species that can cause DNA damage and mutations in the prostate cells.

These mutations can activate the oncogenes that promote cell proliferation and inhibit the tumor suppressor genes that regulate cell division. They can also affect the DNA repair systems, making the cells more susceptible to further damage and mutations.

2. Inflammation-Induced Cell Proliferation and Survival

The inflammatory cells and molecules can stimulate the cancer cells’ survival and proliferation pathways.

The cytokines, such as interleukin-6 and tumor necrosis factor-alpha, can activate the STAT3 and NF-kB transcription factors that promote cell proliferation and survival. The chemokines, such as CCL2 and CXCL8, can recruit and activate the immune cells and promote their infiltration into the tumor microenvironment.

The growth factors, such as epidermal growth factor and insulin-like growth factors, can stimulate the cancer cells’ growth and division.

3. Immunomodulation and Immune Evasion

Chronic inflammation can modulate the immune system’s response to cancer cells, making it less efficient in killing them. The inflammatory cells and molecules can suppress the anti-tumor immune response and promote the pro-tumor immune response.

They can inhibit the activity of the cytotoxic T cells and natural killer cells, which are responsible for destroying the cancer cells. They can also promote the activity of the regulatory T cells and myeloid-derived suppressor cells, which suppress the immune response and create an immunosuppressive microenvironment that allows the cancer cells to evade the immune system.

4. Tissue Remodeling and Angiogenesis

Chronic inflammation can alter the prostate tissue microenvironment, making it more hospitable for the cancer cells to grow.

The inflammatory cells and molecules can stimulate the formation of new blood vessels, promoting the cancer cells’ nutrient and oxygen supply.

They can also promote the production of extracellular matrix molecules and enzymes, such as matrix metalloproteinases and cathepsins, that can degrade the tissue barrier and facilitate the cancer cells’ invasion and migration to other parts of the body.

The Importance of Treating Chronic Inflammation in Prostate Cancer

Given the critical role of chronic inflammation in prostate cancer initiation and progression, it is essential to address inflammation as a therapeutic target.

Several strategies can help mitigate chronic inflammation’s effects and restore the immune system’s balance in the prostate gland.

These strategies include: – Anti-inflammatory agents: Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors can help reduce inflammation and inhibit the production of prostaglandins that contribute to inflammation and carcinogenesis. – Immune modulators: Immune checkpoint inhibitors, such as PD-1 and CTLA-4 blockers, can stimulate the anti-tumor immune response and promote the activity of the cytotoxic T cells and natural killer cells.

– Antioxidants: Natural antioxidants, such as curcumin, resveratrol, and green tea, can scavenge the free radicals and reactive oxygen species and protect the prostate cells from oxidative stress and DNA damage. – Lifestyle modifications: Lifestyle changes, such as exercise, stress reduction, and a healthy diet, can help reduce inflammation and promote immune system health.

Conclusion

Chronic inflammation has emerged as a critical factor in prostate cancer initiation and progression.

The complex interactions between the immune system, inflammation, and cancer in the prostate gland present multiple mechanisms by which chronic inflammation can promote prostate cancer growth and spread. Addressing chronic inflammation as a therapeutic target can help mitigate its effects and restore immune system balance in the prostate gland.