Decreased expression of uroplakin Ia is associated with colorectal cancer progression and poor survival of patients.

AIM: The present study was to investigate the clinical significance of Uroplakins Ia (UPKIa) in the development of colorectal cancer. METHODS: mRNA levels of UPKIa in paired colorectal cancer lesions and the adjacent noncancerous tissues were examined using real-time PCR. The expression and prognostic value of UPKIa were examined in 125 colorectal cancer patients after resection. Statistical analyses were applied to derive prognostic associations. RESULTS: UPKIa mRNA level was down-regulated in colorectal cancer lesions compared with that in the paired adjacent noncancerous tissues. Reduced expression of UPKIa was significantly associated with clinical staging (P = 0.038), and tumor size (P = 0.035) of the disease. Moreover, low expression of UPKIa was significantly associated with poorer overall (OS) and recurrent free (RFS) survival (P = 0.017 and P = 0.007, respectively) of colorectal cancer patients. Multivariate analysis suggested that reduced expression of UPK1a was an independent prognostic marker of colorectal cancer (P = 0.047). CONCLUSIONS: Low expression of UPKIa was a promising predictor for poor outcome of colorectal cancer patients. Further studies on the potential use of UPKIa as a therapeutic targetis are still needed.

Surfactant protein D inhibits adherence of uropathogenic Escherichia coli to the bladder epithelial cells and the bacterium-induced cytotoxicity: a possible function in urinary tract.

The adherence of uropathogenic Escherichia coli (UPEC) to the host urothelial surface is the first step for establishing UPEC infection. Uroplakin Ia (UPIa), a glycoprotein expressed on bladder urothelium, serves as a receptor for FimH, a lectin located at bacterial pili, and their interaction initiates UPEC infection. Surfactant protein D (SP-D) is known to be expressed on mucosal surfaces in various tissues besides the lung. However, the functions of SP-D in the non-pulmonary tissues are poorly understood. The purposes of this study were to investigate the possible function of SP-D expressed in the bladder urothelium and the mechanisms by which SP-D functions. SP-D was expressed in human bladder mucosa, and its mRNA was increased in the bladder of the UPEC infection model in mice. SP-D directly bound to UPEC and strongly agglutinated them in a Ca(2+)-dependent manner. Co-incubation of SP-D with UPEC decreased the bacterial adherence to 5637 cells, the human bladder cell line, and the UPEC-induced cytotoxicity. In addition, preincubation of SP-D with 5637 cells resulted in the decreased adherence of UPEC to the cells and in a reduced number of cells injured by UPEC. SP-D directly bound to UPIa and competed with FimH for UPIa binding. Consistent with the in vitro data, the exogenous administration of SP-D inhibited UPEC adherence to the bladder and dampened UPEC-induced inflammation in mice. These results support the conclusion that SP-D can protect the bladder urothelium against UPEC infection and suggest a possible function of SP-D in urinary tract.