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Flashcards in Cell-cell and cell matrix interactions flashcards Deck (21):
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4 ECM components

1. Collagen fibers 2. Elastin fibers 3. Proteoglycans 4. Multiadhesive matrix proteins

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3 multiadhesive matrix proteins

1. Fibronectin 2. Laminin 3. Perlecan

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Fibronectin

Multiadhesive matrix glycoprotein that binds to integrins

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Laminin

Multiadhesive matrix major protein of ECM and basement membrane. Several functional domains which bind to cells, collagen, and other molecules-therefore can bind cells to basement membrane.

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Perlecan

Multiadhesive matrix proteglycan which binds to and cross-links ECM components and cell-surface molecules

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4 cell-adhesion molecules (CAMs)

1. Cadherins 2. Selectins 3. Integrins 4. Immunoglobin (Ig) superfamily

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Cadherins

Calcium-dependent glycoproteins which mediate zonula adherens. Intracellular, transmembrane, and intercellular domains. 3 types: E (epithelial) cadherins, P (placental) cadherins, N (neural) cadherins. Use trypsin or EDTA (which bind calcium) to dissociate cells.

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Adapter proteins

Act as linkers that directly or indirectly connect cadherins to the cytoskeleton. Recruit intracellular molecules for signaling.

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Alpha and beta catenin

Types of adapter proteins which act as linkers that directly or indirectly connect cadherins to the cytoskeleton

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Cadherins in cancer (3)

1. E-cadherin down-regulated and increases cellular motility, allowing cancer cells to cross basement membrane 2. Loss of E cadherin-->disintegration of cadherin-catenin complex-->Release of signal molecules that may be involved in cell invasiveness 3. N-cadherin is often up-regulated in breast cancer (not usually expressed in mammory epithelium). An N-cadherin antagonist showed dispuption of tumor vasculature, tumor growth inhibition, and apoptosis in tumor cells.

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Selectins

Calcium-dependent glycoproteins produced by endothelial cells and involved in inflammatory process. 3 types: E-selectin (endothelial-leukocyte adhesion molecule), P-selectin (recruitment of platelets), L-selectin (on leukocytes)

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Process of selectin production

Foreign substance-->Macrophages produce cytokines-->stimulate Endothelial cells which produce selectins

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How do endothelial cells recruit leukocytes?

E selectins recognize the carbohydrate and E and P selectins interact with leukocytes and slow them down, causing them to roll along vessel wall near infection site

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Selectins and cancer

Overexpression of E-selectin in vascular endohelium associated with positive lymph node metastasis in breast cancer. Down-regulation of E-selectin correlates with reduction in adhesion of breast cancer cells.

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Integrins

Cell surface glycoproteins which act as receptors for any of the ECM components. Intracellular, transmembrane, and intercellular domains. Attach intracellular adapter proteins that mediate cytoskeleton microfilament attachment and activate adhesion-dependent bidirectional signals.

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3 steps in extravasation of leukocytes

Integrins control organization of cytoskeleton for this to occur 1. E and P selectins weakly bind and cause leukocyte to roll along surface 2. ICAM-1 (Ig family) binds tightly to integrins on leukocyte surface stopping them from rolling 3. Leukocytes secrete proteases and squeeze through endothelium, breaking through basement membrane.

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Leukocyte-adhesion deficiency

Rare genetic defect in synthesis of integrin subunit. Susceptible to infection, poor wound healing because leukocytes cannot extravasate, migrate, and phagocytose bacteria properly.

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Integrins in cancer (3)

1. Integrin activation down-regulates E cadherins 2. modulate expression/activity of MMPs (break down matrix) 3. Target for cancer therapy

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Ig superfamily

Transmembrane proteins with multiple Ig domains (repeats) in extracellular regions. Involved in immune system and in recognition, binding, and adhesion of cells. Share features with antibodies.

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Pemphigus

Autoantibodies produced against either a particular integrin or laminin in matrix. Body attacks itself resulting in blisters all over the body.

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Laminins in cancer (3)

1. Abnormal expression of one of the lamins is hallmark for tumor which may invade colon, breast, and skin cancer cells 2. In normal tissues laminin-332 acts to attach cells to basement membrane via hemidesmosomes and inhibit movement. In some tumors laminin-332 functions to promote migration (difficult to treat because don't want to harm the healthy laminin-332 processes) 3. Elevated laminin-332 poor diagnostic factor in cervical cancer