Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Furthermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion

A Description of the FINRISK 1992 and 1997 Cohorts

<p>Compared to FINRISK-92, the FINRISK-97 cohort includes an additional sample of individuals aged 65–74 y. Numbers for this additional sample are described at the right-hand side for each endpoint. Persons examined refers to cohort individuals for whom information on smoking, blood pressure, cholesterol, and DNA, as well as consent for the use of DNA to study CHD and stroke, were available. Subcohorts are stratified random samples of the original cohorts including also cases. Mortality cases show total mortality, including also those who died from CHD or stroke. Thus, numbers in the boxes of subcohorts and outcome events are not mutually exclusive (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020069#pgen-0020069-t001" target="_blank">Table 1</a>). F, females; M, males.</p