Realtime visualization of tumor cell/endothelial cell interactions during transmigration across the endothelial barrier.
OBJECTIVE
In cancer the blood-borne spread of tumor cells leads to the formation of secondary tumors at distant loci whereby the extravasation of tumor cells is a prerequisite step during hematogenous metastasis. Here, we describe a novel in vitro realtime model which shows the complete sequence of the extravasation process.


METHODS
We developed an in vitro system allowing us to monitor the sequence of extravasation events of tumor cell clusters across a monolayer of human umbilical cord endothelial cells (HUVEC). Fluorescence markers and laser scanning confocal microscopy were used to visualize the interactions between tumor cells and endothelium.


RESULTS
Our model indicates that the extravasation of tumor cell clusters derived from the invasive human bladder carcinoma cell line T24 occurs in a relatively short time-frame up to 4 h after adhesion to the endothelium. We demonstrate that the vascular endothelium is irreversibly damaged at the site of tumor cell extravasation.


CONCLUSIONS
Realtime laser scanning confocal microscopy leads to a better understanding of the complex and dynamic cell-to-cell and cell-to-matrix interactions during the extravasation process.
Heyder
C
C
Institute of Immunology, University of Witten/Herdecke, Stockumer Strasse 10, 58448 Witten, Germany. cheyder@uni-wh.de
Gloria-Maercker
E
E
Entschladen
F
F
Hatzmann
W
W
Niggemann
B
B
Zänker
K S
KS
Dittmar
T
T
D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005110:Extracellular Space / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating / Q000473:pathology / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology