Galectin-4 Reduces Migration and Metastasis Formation of Pancreatic Cancer Cells
- Authors
- Belo, A.I., van der Sar, A.M., Tefsen, B., and van Die, I.
- ID
- ZDB-PUB-130711-3
- Date
- 2013
- Source
- PLoS One 8(6): e65957 (Journal)
- Registered Authors
- van der Sar, Astrid M.
- Keywords
- none
- MeSH Terms
-
- Adenocarcinoma/pathology*
- Cell Line, Tumor
- Galectin 4/genetics
- Galectin 4/physiology*
- Humans
- Neoplasm Metastasis*
- Pancreatic Neoplasms/pathology*
- RNA, Messenger/genetics
- Real-Time Polymerase Chain Reaction
- PubMed
- 23824659 Full text @ PLoS One
Galectin-4 (Gal-4) is a member of the galectin family of glycan binding proteins that shows a significantly higher expression in cystic tumors of the human pancreas and in pancreatic adenocarcinomas compared to normal pancreas. However, the putative function of Gal-4 in tumor progression of pancreatic cancer is still incompletely understood. In this study the role of Gal-4 in cancer progression was investigated, using a set of defined pancreatic cancer cell lines, Pa-Tu-8988S (PaTu-S) and Pa-Tu-8988T (PaTu-T), as a model. These two cell lines are derived from the same liver metastasis of a human primary pancreatic adenocarcinoma, but differ in their growth characteristics and metastatic capacity. We demonstrated that Gal-4 expression is high in PaTu-S, which shows poor migratory properties, whereas much lower Gal-4 levels are observed in the highly metastatic cell line PaTu-T. In PaTu-S, Gal-4 is found in the cytoplasm, but it is also secreted and accumulates at the membrane at sites of contact with neighboring cells. Moreover, we show that Gal-4 inhibits metastasis formation by delaying migration of pancreatic cancer cells in vitro using a scratch assay, and in vivo using zebrafish (Danio rerio) as an experimental model. Our data suggest that Gal-4 may act at the cell-surface of PaTu-S as an adhesion molecule to prevent release of the tumor cells, but has in addition a cytosolic function by inhibiting migration via a yet unknown mechanism.