?2 Integrin-Dependent Suppression of Pancreatic Adenocarcinoma Cell Invasion Involves Ectodomain Regulation of Kallikrein-Related Peptidase-5.

ABSTRACT: Previous reports demonstrate that the ?2-integrin (?2) mediates pancreatic ductal adenocarcinoma (PDAC) cell interactions with collagens. We found that while well-differentiated cells use ?2 exclusively to adhere and migrate on collagenI, poorly differentiated PDAC cells demonstrate reduced reliance on, or complete loss of, ?2. Since well-differentiated PDAC lines exhibit reduced in vitro invasion and ?2-blockade suppressed invasion of well-differentiated lines exclusively, we hypothesized that ?2 may suppress the malignant phenotype in PDAC. Accordingly, ectopic expression of ?2 retarded in vitro invasion and maintenance on collagenI exacerbated this effect. Affymetrix profiling revealed that kallikrein-related peptidase-5 (KLK5) was specifically upregulated by ?2, and reduced ?2 and KLK5 expression was observed in poorly differentiated PDAC cells in situ. Accordingly, well-differentiated PDAC lines express KLK5, and KLK5 blockade increased the invasion of KLK5-positive lines. The ?2-cytoplasmic domain was dispensable for these effects, demonstrating that the ?2-ectodomain and KLK5 coordinately regulate a less invasive phenotype in PDAC.

SUBMITTER: Lee CY 

PROVIDER: S-EPMC3245846 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature