Adhesion of human breast cancer cell line MCF-7 to human vascular endothelial cells in culture. Enhancement by activated platelets.
The interactions of MCF-7 tumor cells with human vascular endothelial cells (EC) and subendothelial extracellular matrices (ECM) were morphologically observed by electron microscopy and quantitatively evaluated by labelling tumor cells with 111Indium-oxine. MCF-7 tumor cells adhered more rapidly to ECM than to the apical surface of a confluent monolayer of EC. The affinity of MCF-7 cells for type-IV collagen was greater than for fibronectin, suggesting that type-IV collagen contributes to the higher rate of adhesion of MCF-7 cells to the subendothelial ECM. Otherwise, the attachment of tumor cells to EC was increased in the presence of both washed platelets and 0.1% citrated platelet-poor plasma (cPPP), a condition accelerating platelet aggregation by tumor cells. The enhancement of MCF-7 adhesion to EC in the presence of platelets and cPPP was completely blocked by the addition of prostacyclin, or hirudin, a specific thrombin inhibitor. In ultrastructural studies, MCF-7 initiated EC retraction, and firm attachment and flattening occurred on exposed ECM. When MCF-7 cells were incubated with platelets and cPPP, most of the tumor cells adhering to the EC and inducing disruption of endothelial monolayer were closely packed and associated with platelet aggregates. MCF-7 cells appeared to adhere more efficiently to exposed subendothelial ECM when they were associated into multicellular aggregates containing platelets and trapped in a fibrin thrombus. Thus, this homologous human system of cultured vascular EC and breast carcinoma line MCF-7 cells may be used to assess anti-aggregant compounds for their ability to alter tumor-cell implantation on EC-lined surfaces.
Abecassis
J
J
Centre Régional de Lutte contre le Cancer Paul Strauss, Strasbourg, France.
Millon-Collard
R
R
Klein-Soyer
C
C
Nicora
F
F
Fricker
J P
JP
Beretz
A
A
Eber
M
M
Muller
D
D
Cazenave
J P
JP
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion; D002453:Cell Cycle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D004837:Epinephrine / Q000494:pharmacology; D005109:Extracellular Matrix / Q000648:ultrastructure; D005260:Female; D005340:Fibrinogen / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009842:Oligopeptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000037:antagonists & inhibitors
D006629:Hirudins; D009842:Oligopeptides; C035202:H-D-Phe-Pro-arginal; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D006493:Heparin; D013917:Thrombin; D004837:Epinephrine