A recent study from the University of Nebraska Medical center shows that cytoplasmic Human antigen R (HuR) plays an important role in cell proliferation, progression, and survival of bladder cancer patients. The findings may lead to more effective prognoses and prediction of bladder and other cancer cases.

HuR is known to be a multifunctional protein that is involved with the regulation of lymphangiogenesis, the formation of lymphatic vessels, and angiogenesis, the formation of blood vessels. However, the relationship between HuR expression and HuR-associated factors in cancer is unclear. Because HuR shuttles between cytoplasm and nuclei, it is important to clarify its pathological significance and prognostic value in both cytoplasmic and nucleic expressions.

The study was conducted on 122 cancer specimens from bladder cancer patients and 20 control specimens, as well as mouse models consisting of 10 samples of normal urothelial cells and 5 chemically induced bladder cancer specimens. Using an HuR antibody from rabbits, known to be reactive in both human and mouse HuR, researchers were able to evaluate HuR expression with an immunoreactive score. The score was judged by cytoplasmic and nuclear staining patterns and evaluated as either low expression (no staining or weak staining), or high expression (moderate or strong staining).

Statistical analysis showed no relationship between pathological features and nuclear HuR expression. Conversely, cytoplasmic HuR expression was positively associated with enzymes involved with vascular growth (VEGF-A and VEGF-C), and an anti-inflammatory enzyme (COX-2). Nuclear HuR expression was also not shown to predict cancer recurrence, metastasis, or cause-specific survival. However, cytoplasmic HuR expression was a significant predictor in each of these parameters. The findings in this report are probably the first to show the relationship between HuR expression and pathological features, recurrence, and survival in patients with bladder cancer.

The regulation of angiogenesis and lymphangiogenesis by HuR is incompletely understood at best. However, this study should strengthen identification of pathological features and support predictive efforts. The HuR related molecules VEGF-A and VEGF-C have been previously associated with human bladder cancer tissues. Noting the statistical disparity between nucleic and cytoplasmic HuR expression, this study implies that the shuttling between the nucleus and cytoplasm is an important process in stimulating angiogenesis and lymphangiogenesis.  Future studies building upon these findings will hopefully further our predictive capabilities. In addition to bladder cancer, high HuR expression has been associated with poor survival rates in cases of colon cancer, breast cancer, and renal cell carcinoma.