T. Maemura

The role of Mac-1 (CD11b/CD18) in osteoclast differentiation induced by receptor activator of nuclear factor-κB ligand

Multinuclear osteoclasts are derived from CD11b‐positive mononuclear cells in bone marrow and in circulation. FACS sorting experiments showed impaired osteoclastogenesis in RAW264.7 cells with low CD11b expression. Neutralizing antibodies and siRNA against CD11b inhibited osteoclastogenesis induced by RANKL. Although primary cultured mouse bone marrow macrophages expressed CD11a and CD11b, osteoclastogenesis induced by M‐CSF and RANKL was inhibited in the presence of anti‐CD11b or anti‐CD18 but not anti‐CD11a antibodies. Furthermore, anti‐CD11b antibodies inhibited NFATc1 expression induced by M‐CSF and RANKL in BMMs. These findings suggest, at least partly, an important role of CD11b in osteoclastogenesis.

The reduction in pigment epithelium-derived factor is a sign of malignancy in ovarian cancer expressing low-level of vascular endothelial growth factor

Background. Angiogenesis is a critical factor in the progression of solid tumors and metastasis. The aim of this study was to characterise the roles of angiogenic and anti-angiogenic factors on ovarian cancer. Methods. The expression levels of vascular endothelial growth factor (VEGF, angiogenic factor) and pigment epithelial growth factor (PEDF, anti-angiogenic factor) were measured by real-time polymerase chain reaction and Western blotting in ovarian tumors. Microvessel density (MVD) was evaluated by the total microvessel length in high-power field of tumor tissue preparations. Results. MVD correlated with tumor malignancy. The tissues with the highest expression levels of VEGF (VEGF-H) were malignant tumors. The VEGF expression levels in some malignant tumors (VEGF-L) were as low as that in benign tumors. Therefore, the expression of PEDF was examined. The PEDF expression levels in VEGF-L malignant tumors were significantly lower than those in benign tumors. On the other hand, the PEDF expression levels in VEGF-H malignant tumor tissues were not significantly different from those in benign tumors. Conclusion. The reduction in PEDF expression levels may be, in part, responsible for tumor malignancy in VEGF-L ovarian tumors. Furthermore, PEDF may be a useful marker of malignancy in VEGF-L ovarian tumors.