https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Matrix Metalloproteinases: Regulators of the Tumor Microenvironment

Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.

Type XIII collagen is a type II transmembrane protein found at many sites of cell adhesion in tissues. Homologous recombination was used to generate a transgenic mouse line (Col13a1 N/N ) that expresses N-terminally altered type XIII collagen molecules lacking the short cytosolic and transmembrane domains but retaining the large collagenous ectodomain. The mutant molecules were correctly transported to focal adhesions in cultured fibroblasts derived from the Col13a1 N/N mice, but the cells showed decreased adhesion when plated on type IV collagen. These mice were viable and fertile, and in immunofluorescence stainings the mutant protein was located in adhesive tissue structures in the same manner as normal 1(XIII) chains. In immunoelectron microscopy of wild-type mice type XIII collagen was detected at the plasma membrane of skeletal muscle cells whereas in the mutant mice the protein was located in the adjacent extracellular matrix. Affected skeletal muscles showed abnormal myofibers with a fuzzy plasma membrane-basement membrane interphase along the muscle fiber and at the myotendinous junctions, disorganized myofilaments, and streaming of z-disks. The findings were progressive and the phenotype was aggravated by exercise. Thus type XIII collagen seems to participate in the linkage between muscle fiber and basement membrane, a function impaired by lack of the cytosolic and transmembrane domains. (Am J Pathol 2001, 159:1581–1592)

Animal Model Lack of Cytosolic and Transmembrane Domains of Type XIII Collagen Results in Progressive Myopathy

The binomial nervous system involves the central nervous system (CNS), comprising the brain and the spinal cord, and the peripheral nervous system (PNS). Both divisions of the nervous system contain electrically excitable neurons as well as a number of supporting neuroglial cells, which include oligodendrocytes, astrocytes, microglia, choroid plexus ependymal cells in the CNS, and satellite and Schwann cells in the PNS. Connective tissues rich in fibrillar collagens form the outermost cover for the nervous system proper. Moreover, there are rich basement membranes (BM) surrounding all nervous system tissues and vessels within these structures. BMs compartmentalize nervous tissues and contribute to selective barrier and filtration functions essential for brain homeostasis. While BMs are absent from the brain parenchyma, there are extracellular matrices (ECM) in these regions that remain under-explored. The composition and types of matrices differ substantially in different parts of the nervous system. ECMs are significantly abundant during development, guiding cellular migration and differentiation as well as axon navigation and synaptogenesis. Additionally, ECMs promote neuronal health, contribute to synaptic homeostasis and plasticity, and are upregulated in response to disease and trauma. It is for these reasons that the mutation and malfunction of collagens have been linked to neurodevelopmental, degenerative, and psychiatric disorders as well as motor and sensory dysfunction. In recent years, it has become clear that collagens, constituting a major family of ECM proteins, and other extracellular components are generated not only by glial cells but also by neurons. The functions and expression patterns of the collagen superfamily members in the nervous system are summarized in this chapter, where we focus on their roles in vitro and in vivo in a number of animal models, and in human diseases of the nervous system.

Collagens as New Players in Nervous System Diseases

In addition to the important structural function in supporting tissues, extracellular matrix regulates the responses of cells to their environment during development, cellular division, maturation and differentiation, migration of cells from one site to another, in the homeostasis of the body and in cancer cell invasion. An essential group of extracellular matrix molecules, the matrisome, is formed by approximately 300 molecules that can be grouped into collagens, proteoglycans and glycoproteins. Information obtained from the synthesis of collagens and gene defects can be utilized in the development of diagnostics and treatment methods for hereditary diseases.

Many dimensions of extracellular matrix research

The α1 Chain of Type XIII Collagen

Type XIII collagen is a focal adhesion protein with possible adhesive function

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