Calreticulin is a highly conserved endoplasmic reticulum chaperone protein which participates in various cellular processes. It was first identified as a Ca2+-binding protein in 1974. Accumulated evidences indicate that calreticulin has great impacts for the development of different cancers and the effect of calreticulin on tumor formation and progression may depend on cell types and clinical stages. Cell surface calreticulin is considered as an “eat-me” signal and promotes phagocytic uptake of cancer cells by immune system. Moreover, several reports reveal that manipulation of calreticulin levels profoundly affects cancer cell proliferation and angiogenesis as well as differentiation. In addition to immunogenicity and tumorigenesis, interactions between calreticulin and integrins have been described during cell adhesion, which is an essential process for cancer metastasis. Integrins are heterodimeric transmembrane receptors which connect extracellular matrix and intracellular cytoskeleton and trigger inside-out or outside-in signaling transduction. More and more evidences reveal that proteins binding to integrins might affect integrin-cytoskeleton interaction and therefore influence ability of cell adhesion. Here, we reviewed the biological roles of calreticulin and summarized the potential mechanisms of calreticulin in regulating mRNA stability and therefore contributed to cancer metastasis.

Bladder cancer is a common urothelial cancer. Through proteomic approaches, calreticulin (CRT) was identified and proposed as a urinary marker for bladder cancer. CRT is a multifunctional molecular chaperone that regulates various cellular functions such as Ca(2+) homeostasis and cell adhesion. CRT is overexpressed in various cancers, but its mechanism of action in the development of bladder tumors remains unclear. We generated J82 bladder cancer cells lines that either stably overexpressed or knocked down CRT to investigate the physiological effects of CRT on bladder tumors. Compared with the transfected control vector cells, the knockdown of CRT suppressed cell proliferation, migration, and attachment, whereas overexpression of CRT enhanced cell migration and attachment. We further demonstrated that the phosphorylation status of focal adhesion kinase and paxillin, important regulators of the focal adhesion complex, was also regulated in these cells. In contrast, phosphorylation of Src, a protein tyrosine kinase reported to be affected by CRT, was not significantly different between the control and CRT-RNAi groups. Most importantly, we observed that tumors derived from J82 CRT-RNAi cells were significantly smaller and had fewer metastatic sites in the lung and liver in vivo than did transfected control vector cells. In conclusion, our results suggest that alteration of CRT expression levels might affect bladder cancer progression in vitro and in vivo.

Diagnosis of osteoporosis is based on bone mineral density (BMD) measurement, which is site dependent and commonly discordant between measurement sites. We aimed to determine the prevalence of osteoporosis diagnosed based on BMD T-scores measured by dual-energy x-ray absorptiometry (DXA) at different sites: the lumbar spine (LS) alone, femoral neck (FN) alone, or both. A total of 1712 women and 2028 men with LS and FN BMD measurements were enrolled. Over 50% discordance was found between osteoporosis classifications based on T-scores measured at the LS and FN. Use of the lowest T-scores measured at both the LS and right and left FN (rather than one site) significantly increased the prevalence of osteoporosis from 4.03 to 10.75% in postmenopausal women and 1.82 to 4.29% in men aged ≧50 years (p < 0.001). The trends of overall and age-adjusted prevalence of osteoporosis were similar in women and men. Osteoporosis was diagnosed at a higher rate if the USA reference rather than the Asia reference was used to calculate the T-score (26.64% vs. 10.75%). In conclusion, diagnosis based on the lowest T-score from multiple site BMD measurement can increase the prevalence of osteoporosis, demonstrating the higher sensitivity of the multiple site measurement strategy.