Cell-cell and cell matrix interactions flashcards

Question 1

4 ECM components

Answer 1

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

Question 2

3 multiadhesive matrix proteins

Answer 2

1. Fibronectin 2. Laminin 3. Perlecan

Question 3

Fibronectin

Answer 3

Multiadhesive matrix glycoprotein that binds to integrins

Question 4

Laminin

Answer 4

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.

Question 5

Perlecan

Answer 5

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

Question 6

4 cell-adhesion molecules (CAMs)

Answer 6

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

Question 7

Cadherins

Answer 7

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.

Question 8

Adapter proteins

Answer 8

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

Question 9

Alpha and beta catenin

Answer 9

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

Question 10

Cadherins in cancer (3)

Answer 10

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.

Question 11

Selectins

Answer 11

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)

Question 12

Process of selectin production

Answer 12

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

Question 13

How do endothelial cells recruit leukocytes?

Answer 13

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

Question 14

Selectins and cancer

Answer 14

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.

Question 15

Integrins

Answer 15

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.

Question 16

3 steps in extravasation of leukocytes

Answer 16

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.

Question 17

Leukocyte-adhesion deficiency

Answer 17

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

Question 18

Integrins in cancer (3)

Answer 18

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

Question 19

Ig superfamily

Answer 19

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.

Question 20

Pemphigus

Answer 20

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

Question 21

Laminins in cancer (3)

Answer 21

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