2 integrin-dependent suppression of pancreatic adenocarcinoma cell invasion involves ectodomain regulation of kallikrein-related peptidase-5

Chia Yao Lee, David Marzan, Grace Lin, Steven Goodison, Steve Silletti

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Previous reports demonstrate that the 2-integrin (α2) 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, α2. Since well-differentiated PDAC lines exhibit reduced in vitro invasion and 2-blockade suppressed invasion of well-differentiated lines exclusively, we hypothesized that α2 may suppress the malignant phenotype in PDAC. Accordingly, ectopic expression of α2 retarded in vitro invasion and maintenance on collagenI exacerbated this effect. Affymetrix profiling revealed that kallikrein-related peptidase-5 (KLK5) was specifically upregulated by α2, and reduced α2 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 α2-cytoplasmic domain was dispensable for these effects, demonstrating that the α2-ectodomain and KLK5 coordinately regulate a less invasive phenotype in PDAC.

Original languageEnglish (US)
Article number365651
JournalJournal of Oncology
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

Kallikreins
Integrins
Adenocarcinoma
Peptide Hydrolases
Tissue Kallikreins
Phenotype
Cell Communication
Collagen
Maintenance

ASJC Scopus subject areas

  • Oncology

Cite this

2 integrin-dependent suppression of pancreatic adenocarcinoma cell invasion involves ectodomain regulation of kallikrein-related peptidase-5. / Lee, Chia Yao; Marzan, David; Lin, Grace; Goodison, Steven; Silletti, Steve.

In: Journal of Oncology, 01.12.2011.

Research output: Contribution to journalArticle

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