α2 Integrin-Dependent Suppression of Pancreatic Adenocarcinoma Cell Invasion Involves Ectodomain Regulation of Kallikrein-Related Peptidase-5
Figure 3
Reexpression of α2 recapitulates collagen interactions and retards invasion. (a) (i) Adhesion of MP2-α2/TC and MP2-α2/CI cells in the presence or absence of function-blocking antibodies directed towards the indicated integrins. (ii) Time course of adhesion of MP2-α2/TC and MP2-α2/CI cells. (iii) Titration of collagenI adhesion of MP2-α2/TC and MP2-α2/CI cells. (iv) Adhesion of MP2-mock and MP2-α2/TC cells to collagenI was compared to the collagenI adhesion of MP2-α2/CI cells that had been grown for the indicated times off collagenI (OffCI). (b) Haptotactic migration time course of MP2-α2/TC and MP2-α2/CI cells on collagenI. (c) In vitro invasion of MP2-mock and week10 MP2-α2/CI cells. (d, left panel) Invasion of MP2-mock and MP2-α2/TC cells was compared with MP2-α2/CI cells after the indicated weeks of culture. (d, right panel) Parental MIAPaCa2 cells were cotransfected pEF4/LacZ reporter and either empty pCDNA3.1 vector (Mock) or the pCDNA3.1/α2 construct, and invasion of LacZ-positive cells examined 48 hours later. (e) Adhesion of MP2-mock, MP2-α2/TC, and MP2-α2/CI cells to a titration of Matrigel. (f) FACS analysis of α2 expression by transiently transfected MP2 cells (α2/48 h) versus stable MP2-α2/TC and MP2-α2/CI cells. (g) CollagenI (CI) and fibronectin (FN) adhesion of mock- or α2-transfected MP2 cells at 48 h versus stable MP2-mock and MP2-α2/TC cells.
