論文

Background: Although matrix metalloproteinases (MMPs) are implicated in tumourigenesis and cancer progression, the role of MMP-13 in melanoma cell metastases is poorly understood. Methods: Lung metastases of mouse melanoma B16BL6 cells were analysed in MMP-13 knockout (KO) and wild-type (WT) mice after intravenous injection. The mRNA and protein expression of MMP-13 in lung tissues was analysed by RT-PCR, real-time PCR, immunoblotting and immunohistochemistry. The expression of SDF-1α, CXCR4 and endostatin, and effects of endostatin to cultured melanoma cells and lung metastases were also studied. Results: Lung metastases of B16BL6 cells were significantly higher by 2.5-5.7-fold in MMP-13 KO mice than in WT mice. The expression of MMP-13 in WT mouse lung tissue was stimulated on day 1 after intravenous injection of the melanoma cells and MMP-13 was immunolocalised to vascular endothelial cells in the lungs. Endostatin formation, but not degradation of SDF-1α, in the lung tissue was associated with reduced lung metastasis in WT mice. Endostatin significantly inhibited migration of B16BL6 cells in monolayer wounding assay and remarkably suppressed Matrigel invasion and transendothelial invasion of the cells. In addition, lung metastases of melanoma cells in MMP-13 KO mice were reduced by intraperitoneal administration of endostatin. Conclusion: Our results suggest that MMP-13 is overproduced by endothelial cells in the lungs with melanoma cells and has a protective role in lung metastasis by local generation of endostatin. © 2011 Cancer Research UK All rights reserved.

It has long been believed that a damaged central nervous system (CNS) is difficult to regenerate; however, as a result of the rapid progress in biomedical science, including stem cell biology, there has been a renewed and an increasing interest in developing regenerative therapies for the CNS. Driving this interest has been the discovery of neural stem cells in the adult mammalian CNS, including the human CNS, and the finding that neurogenesis occurs in the adult brain. To achieve regeneration of a damaged CNS, our main strategies encompass: (1) axonal regeneration, (2) replenishment of lost neural cells, and (3) functional recovery. In this review, achievements using these approaches will be outlined. © 2011 by Lippincott Williams & Wilkins.