The Role of Cell Adhesion in Inflammation and Metastasis 赵燃 丁合

Inflammation Inflammation is one of the primary responses to infection. It is a protective response, but it also produces adverse side effects, such as fever, redness, and pain. Throat Inflammation

A part of the body becomes contaminated by bacteria Leukocytes that would normally remain in the bloodstream will traverse venular endothelial cells and enter the tissue Leukocytes move in response to chemical signals toward the invading microorganisms, which they ingest

How are leukocytes recruited to sites of inflammation? How are they able to stop flowing through the bloodstream and adhere to vessel walls? Three types of cell-adhesion molecule: selectins, integrins and IgSF protein

Step 1:damage tissue, chemical signal, walls of the venules becomes activated Step 2: P-and E-selectins display on the surface of activated endothelial cells, neutrophils encounter the selectins, form adhesions and slow their movement, neutrophils roll slowly along the wall of the vessel Step 3:phospholipid called PAF binds to a receptor, sending a signal into the neutrophils, increase the activity of integrins Step 4: activated intergrins bind with IgSF (ICAM ), neutrophils stop rolling and adhere firmly to the wall of the vessel Step 5: The bound neutrophils change their shape and squeeze between adjacent endothelial cells into the damaged tissue.

Function This cascade of events, which involves several different types of cell-adhesion molecules, ensures that attachment of blood cells to the walls of blood vessels and subsequent penetration will occur only at sites where leukocyte invasion is required

LAD LAD: A rare disease called leukocyte adhesion deficiency Cause: Person with this disease are unable to produce the β 2 subunit as part of a number of leukocyte integrins Characteristics : They lack the ability to adhere to the endothelial layer of venules, they suffer from repeated life- threatening bacterial infections.

Treatment: The disease is best treated by bone marrow transplantation, which provides the patient with stem cells capable of forming normal leukocytes.

The role of cell adhesion in Metastasis

What is cancer?

Metastasis Definition : the spread of a tumor within the body Metastatic cells’ factor : 1.less adhesive 2. Can penetrate numerous barriers 3.can invade normal tissues

Matrix metalloproteinases (MMPs) What is MMPs ? ECM digesting enzymes Function: 1. degrade the proteins and proteoglycans that stand in the way of cancer cell migration 2. cleavage of certain proteins of the ECM by MMPs produces active protein fragments that act back on the cancer cells to stimulate their growth and invasive character.

MMP inhibitors mice: can reduce metastasis human: have little promise in stopping late-stage tumor progression

E-cadherin What is E-cadherin? the predominant cell-adhesion molecule of the adherens junction The lower the level of expression of E-cadherin, the greater the cell’s metastasis potential

Function: 1. favor the adhesion of cells to one another 2. suppress the dispersal of tumors cells to distant sites 3. may also inhibit the signaling pathways within the cells that lead to tissue invasion and metastasis. The important of E-cadherin is evident from a study of a family