Question

In an experiment, cells were growing in a Petri dish that had been coated with Extra-cellular matrix (ECM) components. A peptide added to the dish caused the cells to detach from the ECM on the dish surface. The peptide was a disintegrin.

(a) From the statements below, which one best explains the molecular details of why the cells detached?                            [ Select ]                       ["i", "ii", "iii"]      

(i) Disintegrin competes with the RGD sequence of integrin for binding ECM proteins (such as fibronectin). This disrupts the integrin-ECM association.

(ii) Disintegrin competes with the RGD sequence of ECM proteins (such as fibronectin) for integrin binding. This disrupts the integrin-ECM association.

(iii) Disintegrin binds to the RGD sequence of ECM proteins (such as fibronectin). This disrupts the integrin-ECM association.

(b) Which one of the following is the best explanation for why metastatic cancer cells secrete disintegrin.                            [ Select ]                       ["i", "ii", "iii"]      

(i) Disintegrin prevents cells from interacting with the ECM so that cells can migrate through connective tissue and into the blood stream.

(ii) Cell migration involves focal adhesions that connect cells to the ECM, but hemidesmosomes must be disrupted for a cell to detach from the basal lamina.

(iii) Cell migration involves changes in cadherin expression that allows cells to detach from the tissue and enter the blood stream.

(c) Other factors promote cancer cells to metastasize. For each of the following, decide whether metastasis would be promoted or inhibited.

Secretion of ECM proteases.                            [ Select ]                       ["PROMOTED", "INHIBITED", "", ""]      

Secretion of less fibronectin.                            [ Select ]                       ["PROMOTED", "INHIBITED"]      

Cell-cell interaction with endothelial cells of blood vessels.                            [ Select ]                       ["PROMOTED", "INHIBITED"]      

(d) When a cancer cell reaches a new site in the body, many cancer cell properties are required to allow it to form a new tumor? Decided which factors below would promote the growth of a secondary tumor and which ones would not.

(i) Expression of an integrin that binds to the type of fibronectin that is present at the new site.                            [ Select ]                       ["WOULD", "WOULD NOT"]      

(ii) Expression of FLIP, which resembles procaspase 8 and 10 but lacks a proteolytic domain.                            [ Select ]                       ["WOULD", "WOULD NOT"]      

(iii) Expression of Apaf1.                            [ Select ]                       ["WOULD", "WOULD NOT"]      

Answer 1

a. Answer is option ii.

Like ECM proteins ( fibronectin), disintegrins also posses RGD motif. RGD motif of fibronectin is necessary for integrin binding. Disintegrins compete with RGD sequence of fibronectin for integrin binding and thereby disrupt the cell-ECM interaction.

b. Answer is option i.

Disintegrins secreted by cancer cells disrupt cancer cell interaction with the ECM and help in metastasis.

c. Secretion of ECM proteases - promoted

ECM proteases like Matrix metalloproteinases disrupt the various ECM molecules and help in metastasis.

Secretion of less fibronectin - promoted

Less fibronectin means less interaction of cells with ECM and this helps to make the route for metastasis.

Cell-cell interaction with endothelial cells of blood vessels - inhibited.

If cell-cell interactions increase then there will be less possibility of cancer cells for extravasation and entering into blood stream.

d.i. would.

New expression of integrins will allow cancer cells to interact with the new ECM

ii. Would.

If the FLIP lacks the proteolytic domain then it will remain as procaspase form and would not promote apoptosis of cancer cells.

iii. Would not.

Apaf1 is an important molecule which plays an important role in intrinsic apoptosis pathway.