An in vitro model study of BSp73 rat tumour cell invasion into endothelial monolayer.
In order to study the process of invasion in more detail we developed an in vitro model of the vessel wall. Rat tumour cells derived from an adenocarcinoma of the pancreas, BSp73 AS--of high invasive but low metastatic capacity--and BSp73 ASML--not invasive but highly metastatic--were compared for their mode of invasion into confluent monolayers of endothelial cells. Corneal as well as vascular endothelial cells were plated alternatively onto the basal lamina-like bovine lens capsule that was mounted in a combi-ring dish or reconstituted extracellular matrix (Basement Membrane Matrigel) as substrata. The endothelial monolayers were confronted with AS- and ASML-tumour cells. The interaction of the various cell types was followed by scanning and transmission electron microscopy. The invasive cell type AS was able to force the endothelial cells to retract and subsequently undermined the endothelial cell layer. In the noninvasive cell population ASML most cells remained in the typical roundish morphology and did not interact with the endothelial cell layers. Only a very minor fraction of ASML populations was able to attach to and also invade into the endothelial cell monolayer. It could be shown that AS-cells individually and as small groups penetrated the endothelial cell layer. The results of transmission and scanning electron microscopy suggest that endothelial cell retraction and underlapping of adjacent endothelial cells by tumour cells play an important role in invasion and extravasation through blood vessels. Against all expectations, the nonmetastasizing tumour cell variant (AS-cells) exhibited a dramatic invasive behaviour whereas the highly metastatic ASML-variant mostly retained its spherical shape and showed invasive activity only in exceptional cases.
Boxberger
H J
HJ
Institute of Cell and Tumor Biology, German Cancer Research Center, Heidelberg.
Paweletz
N
N
Spiess
E
E
Kriehuber
R
R
D000230:Adenocarcinoma / Q000473:pathology* / Q000648:ultrastructure; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D046508:Culture Techniques / Q000295:instrumentation / Q000379:methods; D004728:Endothelium, Corneal / Q000166:cytology / Q000473:pathology* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats