The most common tumors in men are genitourinary, with prostate cancer predominating. Genitourinary cancers are fifth most common in women. This review covers the use of hyaluronan or hyaluronic acid (HA) in genitourinary tumors, including prostate, bladder, renal, testicular, penis and Wilms’ tumors. The connection between HA and genitourinary cancer has been studied for 50 years. HA may be predictive and therapeutic for genitourinary tumors.

HA is a glycosaminoglycan. The production of HA is increased by mechanical pressure on cells. It functions in cell division, cell movements, transformation of cells and blood vessel growth in the development of embryos. In adults, it helps wound healing and immune functioning. The adhesiveness of HA makes it useful in wound healing. HA helps maintain cell free spaces. (This property may result in increased metastatic potential.)

HA synthase (HAS) genes are responsible for the enzymes which produce HA. Hyaluronidase (HAase) genes code for enzymes which degrade HA, chondroitin sulfate and chondroitin. The balance of these enzymes determines the rates of progression of genitourinary tumors. Various tests have been used to predict the presence or prognosis of genitourinary tumors. HAase activity is high in squamous cell carcinoma of the head and neck, breast tumors, metastatic tumors and glioma cells.

The genes which control the balance between HAase and HAS are encoded and can be altered by epigenetic events. Genitourinary tumors are related to chromosome abnormalities. HAase is a tumor promoter in doses seen in tumors. At slightly higher levels, HAase is a tumor suppressor.

HA has the property of cell adhesion is shown by its ability of attract circulating lymphocytes (white blood cells) and stop them from circulating. This is believed to promote prostate cancer bone metastases. HA can promote cancer cell migration, also. The adhesiveness has been shown to be important to the metastasis of prostate cancer cells. Blocking the action of HA could be therapeutic in prostate cancer and in renal fibrosis due to kidney cancer. HA promotes tumor cell migration and motility.

Forms of HA have been shown to promote angiogenesis (the formation of new blood vessels). High doses of HA block the same angiogenesis.

CONCLUSION: The increased motility and migration caused by hyaluronic acid (HA) can increase metastatic risk. This has been demonstrated in genitourinary cancers. Hyaluronidase enzymes are being studied for their diagnostic and therapeutic benefits in genitourinary cancers and in other cancers.

NOTE: One HA precursor scavenger is 4-methylumbelliferone. Chamomile (Matricaria chamomilla) contains umbelliferone, which is believed to reduce progression of hyperglycemia and its’ complications. It could reduce the negative effects of HA. Read about the benefit of apigenin in genitourinary cancer, such as prostate cancer. Read about apigenin as a proteasome inhibitor in cancer cells.

Hyaluronic acid could be detrimental in people with genitourinary cancers, such as prostate cancer, and some other cancers, such as breast cancer.

To read the author’s abstract of the article click on the link to the author’s title of the article above.

PMID: 18508614.

Summary #306.