The role of cell adhesion in inflammation and metastasis

Vocabulary Inflammation 引起炎症的 metastasis 转移 leukocytes 白细胞 endothelial layer 内表皮层 venules (small veins) 小静脉 reperfusion damage 再灌流损坏 asthma 哮喘 toxic shock syndrome 毒性休克综合症

respiratory distress syndrome 呼吸窘迫 综合症 Selectins 选择素 Neutrophils 嗜中性粒细胞 Phagocytic 吞噬的 Nonspecific 非特异的 Pathogen 病原体，病菌 Ligand 配体，配基 Synthetic 合成 Endothelium 内皮细胞层

platelet activating factor 血小板活化 因子 Extravasation 外侵 leukocyte adhesion deficiency 白细胞 （ LAD ） 黏附障碍 subunit 亚基 Infection 感染，传染，侵染 Bone marrow transplantation (BMT) 骨髓 移植 Inflammatory 炎症反应 Rheumatoid arthritis 类风湿性关节炎

Thyroid 甲状腺 Malignant tumors 恶性肿瘤 Lymphatic channel 淋巴导管 Penetrate 贯通，渗透 The matrix metallopoteinase (MMPs) 基质金属蛋白水解酶 Degrade 降解 Pharmaceutical industry 医药工业 Clinical trial 临床实验 Encode 将 …… 密码化

Inflammation Metastasis and cancer

Inflammation is one of the primary response to infection. If a part of the body becomes contaminated by bacteria the site of injury becomes a magnet for a variety of white blood cells 伤口  吸引白细胞  黏着  进入组织  作用炎症处

A great deal of research has focused on questions related to these conditions How are leukocytes recruited to sites of inflammation? How are they able to stop flowing through the bloodstream and adhere to vessels ? How can some of the negative side effects of inflammation be blocked without interfering with the beneficial aspects of the response?

????????????? 3 types of cell adhesion molecules Selectins Integrins IgSF proteins

1.the walls of the venules become activated in response to chemical ” signals ” from nearby damaged tissue.

2.a temporary display of P- and E- selectins on the surfaces of the activated endothelial cells in the damaged area.

??????????????? How many known seletins are there ? Name all of them. where are they ? E-selectin, present on endothelial cells P-selectin, present on platelets and endothelial cells L-selectin,present on leukocyte or WBC

3.As the neutrophils interact with the inflamed venule endothelium,an activation process causes an increase in the binding activity of certain integrins already situated on the neutrophil surface

4.The activated integrins then bind with high affinity to IgSF molecules on the surface of the endothelial cells,causing the neutrophils to stop their rolling and adhere firmly to the wall of the vessel.

5.The bound neutrophils then change their shape and squeeze between adjacent endothelial cells into the damaged tissue.

Effects A protective response in general,but can also produce adverse side effects,such as fever,swelling due to fluid accumulation, redness and pain reperfusion damage 再灌流损坏

Effects An overzealous inflammatory response can lead to asthma 哮喘 toxic shock syndrome 毒性休克综合症 and respiratory distress syndrome 呼吸窘迫综合症

leukocyte adhesion deficiency （ LAD ） Unable to produce the β 2 subunit as part of a number of leukocyte integrins

Anti-inflammatory drugs Antibodies against the β 2 Subunit, Blocking the movement of neutrophils and other WBC out of the blood vessels Anti-selectin antibodies and synthetic carbohydrate Interfering with binding of ligands to E-and P-selectins back

Cancer A disease in which cells escape from the body ’ s normal growth control mechanisms and proliferate in an unregulated manner The spread of a tumor within the body is called metastasis

What is cancer? In the normal adult, cells only grow and divide slowly and under very tight control to make sure that the number of cells in each tissue stays the same. Cancer begins when one cells changes and startys growing and dividing rapidly and out of control. This one cells divides to give two cells, then four, eight and so on until they form growing mass of cancer cells - called a tumour.

Can you inherit cancer? Cancer itself cannot be inherited, but some people do inherit a higher risk of getting cancer. This is because they inherit, from their parents, a slightly damaged version of one of the genes involved in controlling cell division. On its own, this damaged gene is not enough to make cells cancerous.

Normally, two or three different genes have to be damaged before a cell will become cancerous. That is why so very few of the billions of cells in our body ever become cancerous. Can you inherit cancer?

However, if someone starts out with every cell in their body carrying damage in one of these genes, the chance of a cell getting the other types of gene damage and becoming cancerous is much higher.

Can you inherit cancer? Some of these inherited damaged genes have been identified, such as BRCA1 and BRCA2 which increase the risk of getting breast cancer by five to seven times.

metastasis Cancer cell

Most types of cancer cells form a lump called a tumor.

For example, the cancer cell will spreads to the bones from the lung. Spread Local tissuesDistant organs

tumor Benign tumor Malignant tumor Cancer (carcinoma) sarcoma

What do malignant and benign mean? In some tumours, the cells stay in the same place and as the tumour stops growing before it gets very large - often because it simply runs out space to grow. These are called benign tumours and they are not normally dangerous. We all have benign tumours, such as moles and warts. However, in other tumours the cells are able to invade the surrounding tissue and spread into nearby organs where they can cause serious and, eventually, fatal damage. These are called malignant tumours.

Matrix metalloproteinases (MMPs) Matrix metalloproteinases (MMPs) are a class of related, yet structurally distinct, zinc-dependent proteases discovered in connection to their capacity to degrade extracellular matrix proteins such as collagen and elastin. While MMP activity is integral to many physiological and pathophysiological processes, including development, wound healing, and tumor metastasis,

MMPs can also degrade the proteins and proteoglycans that stand in the way of cancer cell migration. Way out ? The synthetic MMPs inhibitors

E-cadherin Favor the adhesion of cells to one another and surpress the dispersal of tumor cells to distant sites

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