Promotion of tumor cell migration by extracellular matrix proteins in human pancreatic cancer.
OBJECTIVE
The pathogenesis of pancreatic carcinoma is driven by the tumor cells ability to migrate causing invasion and metastases. The correlation between the aberrant expression of basement membrane proteins and the process of tumor invasion and metastasis has not been fully determined.


METHODS
In the present study, the influence of laminin, fibronectin, and collagen type IV on migratory activity of 5 different cell lines has been investigated at the level of a single tumor cell using 3-dimensional time-lapse microscopy.


RESULTS
All investigated cell lines have shown a high baseline migration that varied between 6.2 +/- 3.6 and 20.6 +/- 6.8 microm/h. The addition of laminin, fibronectin, and collagen type IV to collagen type I matrix has significantly increased tumor cell migration. Tumor cell migration was strongly inhibited after treating the tumor cells with anti-beta1 monoclonal antibodies. An abundant and continuous expression of laminin, fibronectin, and collagen type IV was found on the basement membrane of perineurium, which sharply promoted tumor cell invasion.


CONCLUSIONS
The continuous presentation of the basement membrane proteins by perineurium contributes to the affinity of pancreatic cancer cells for the perineural tumor invasion. Blockade of integrins could represent a possible approach to control the basement membrane-guided tumor spread.
Ryschich
Eduard
E
Department of Surgery, University of Heidelberg, Germany. eduard.ryschich@med.uni-heidelberg.de
Khamidjanov
Akmal
A
Kerkadze
Vachtang
V
Büchler
Markus W
MW
Zöller
Margot
M
Schmidt
Jan
J
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism / Q000494:pharmacology; D024061:Collagen Type III / Q000378:metabolism / Q000494:pharmacology; D024141:Collagen Type IV / Q000378:metabolism / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010525:Peripheral Nerves / Q000378:metabolism; D014183:Transplantation, Heterologous; D019096:Vitronectin / Q000378:metabolism / Q000494:pharmacology
D024042:Collagen Type I; D024061:Collagen Type III; D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D019096:Vitronectin