Naslov
S100P-Binding Protein, S100PBP, Mediates Adhesion through Regulation of Cathepsin Z in Pancreatic Cancer Cells

Autori
Lines, Kate ; Chelala, Claude ; Dmitrović, Branko ; Wijesuriya, Nilukshi ; Kocher, Hermant ; Marshall, John ; Crnogorac-Jurčević, Tatjana

Izvornik
American journal of pathology (0002-9440) 180 (2012), 4; 1485-1494

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
procathepsin-X; adenocarcinoma; expression; cysteine; invasion; binding; matrix GENES
(procathepsin-X; adenocarcinoma; expression; cysteine; invasion; binding; matri)

Sažetak
Several S100 proteins are up-regulated in pancreatic ductal adenocarcinoma (PDAC), the most significant being S100P. We previously reported on S100PBP, a binding partner of S100P, that shows no homology to any described protein and whose functions are completely unknown. To determine S100PBP expression across human tissues and organs, immunohistochemistry was performed using both multiorgan- and inhouse–constructed pancreatic tissue microarrays. To establish S100PBP functions, cell lines with either stably overexpressed or silenced S100PBP were generated and investigated using Affymetrix gene expression arrays and complementary functional assays. We show that S100PBP is differentially expressed in various healthy and tumor specimens, which is both cancer- and tissue-type dependent. In healthy pancreas, S100PBP is expressed in the nuclear/perinuclear region of both exocrine and endocrine compartments. In early precancerous lesions, S100PBP is translocated to the cytoplasm, whereas in PDAC and metastatic lesions, its expression is significantly diminished. The most pronounced phenotypic change after manipulation of S100PBP expression was seen in adhesion ; this was significantly reduced after S100PBP up-regulation and increased after S100PBP silencing. Up- regulation or silencing of S100PBP also led to a concomitant change in the levels of the protease cathepsin Z, the silencing of which significantly reduced PDAC cell adhesion. We further demonstrate that the interaction of cathepsin Z with arginine-glycine-aspartic acid–binding integrins, specifically
v5, mediates the changes seen in adhesion of PDAC cells.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA