Thursday, August 2, 2012

Role of Chemokines in Cancer

Prostate cancer is a serious medical issue in men; this type of cancer is the second deadliest type of cancer and the most frequently diagnosed cancer in males. Scientists have suspected that chemokines are involved in prostate cancer progression, and are now being researched extensively. Chemokines are a type of cytokines that are involved in inflammation and stimulate chemotaxis, also known as movement, of leukocytes, a type of white blood cells.

There are 45 types of chemokines in the human body and they interact with a type of receptor known as a G protein coupled receptor. Many of these chemokines are redundant; multiple chemokines interact with one receptor or multiple receptors interact with one chemokine. After the chemokines interact with a receptor, the receptor induces a signaling cascade that can control a number of different responses in the body.

(Image from: Role of Chemokines in Cancer)

Researchers believe the chemokines play a role in prostate cancer because research has shown that the expression of chemokines changes when the prostate changes from normal to benign prostatic hyperplasia (BPH) and finally, to prostate cancer itself. Most of the research being conducted on chemokines has been on CXCL8, CXCL12, and CCL2. Recent studies have shown that CXCL8 levels are higher in patients with BPH than in patients with a normal prostate. Additionally, the CXCL8 RNA levels increased in patients with an increased severity of prostate tumors. In patients with recurring prostate cancer, CXCL8 has been found in benign areas near the cancerous tumors, but it has not been found in benign areas in patients without cancer recurrence.

The chemokine, CXCL12, and its receptor, CXCR4, have also exhibited correlations with prostate cancer. Both CXCL12 and CXCR4 were higher in patients’ tissue with prostate cancer compared to patients’ tissue with BPH. Also, patients with a higher number of CXCR4 receptors expressed in tumors demonstrated a lower survival expectation than patients with a lower number of receptors.

In addition to affecting the cancer itself, chemokines have an impact on the incidence of prostate cancer. African American men with prostate cancer have higher levels of CCL5, CCRT, and CXCR4 in their cancerous tumors, as compared to European American men with prostate cancer. Correspondingly, African American men have a higher incidence of prostate overall, as compared to other male racial populations. As physicians and many patients are aware of, age also plays a important factor in the development of prostate cancer. Older prostate stromal fibroblasts, common cells present in all patients’ prostates, exhibit higher levels of CXCLR, when compared to younger prostate fibroblasts.

While there still remains much research to be done, scientists now know that chemokines are involved somehow in the progression of . These chemokines and their receptors regulate the invasion and infiltration of cells, such leukocytes, and the growth of cancerous cells and blood vessels. However, the actual signals and regulation of the chemokines in prostate cancer are not well understood. Additionally, not all of the chemokines have been studied in prostate cancer, and many chemokines are most likely involved in the disease progression. Based on the existing research, it is clear that these chemokines exist as prostate cancer markers and may serve as potential therapeutic targets for cancer treatments.

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