Mechanical stimulations can inhibit local and remote tumor progression by downregulating WISP1.

Mechanical stimulations can prevent bone loss, but their effects on the tumor-invaded bone or solid tumors are elusive. Here, we evaluated the effect of knee loading, dynamic loads applied to the knee, on metastasized bone and mammary tumors. In a mouse model, tumor cells were inoculated to the mammary fat pad or the proximal tibia. Daily knee loading was then applied and metabolic changes were monitored mainly through urine. Urine samples were also collected from human subjects before and after step aerobics. The result showed that knee loading inhibited tumor progression in the loaded tibia. Notably, it also reduced remotely the growth of mammary tumors. In the urine, an altered level of cholesterol was observed with an increase in calcitriol, which is synthesized from a cholesterol derivative. In urinary proteins, knee loading in mice and step aerobics in humans markedly reduced WNT1-inducible signaling pathway protein 1, WISP1, which leads to poor survival among patients with breast cancer. In the ex vivo breast cancer tissue assay, WISP1 promoted the growth of cancer fragments and upregulated tumor-promoting genes, such as Runx2, MMP9, and Snail. Collectively, the present preclinical and human study demonstrated that mechanical stimulations, such as knee loading and step aerobics, altered urinary metabolism and downregulated WISP1. The study supports the benefit of mechanical stimulations for locally and remotely suppressing tumor progression. It also indicated the role of WISP1 downregulation as a potential mechanism of loading-driven tumor suppression.

ELISA of CCN Family Proteins in Body Fluids Including Serum and Plasma.

Enzyme-linked immunosorbent assay (ELISA) is the most popular methodology for absolute quantification of particular proteins in liquid samples. Especially for CCN family members that are associated with human diseases, utility of ELISA for those proteins in clinics as well as research laboratories is emphasized. However, in order to obtain accurate and stable results in ELISA, particular care should be taken in controlling the quality and quantity of standard CCN family proteins, which bind to various materials and can be unstable in a purified form. Recently, diagnostic value of the CCN family protein fragments in body fluids has been indicated in several diseases. Therefore, module-specific detection system for the CCN family members is desired as a promising tool in clinics. It should be also noted that modular fragments of CCN family members can be more stable than the full-length in purified forms, whose quality may be easier to control than that of the full-length ones.