Increase in fluidity in the membrane of MT3 breast cancer cells correlates with enhanced cell adhesion in vitro and increased lung metastasis in NOD/SCID mice.
To study whether membrane fluidity of tumor cells have an influence on metastasis, MT3 breast cancer cells harvested during exponential growth and under confluent conditions were compared. Electron paramagnetic resonance (EPR) data revealed that, in comparison to growing cells, confluent cells have a significant higher fluidity in their membrane related to a higher relative portion of disordered domains and a reduced portion of the most ordered domains. Further, sialyl Lewis X and/or A ligand-mediated adhesion of these cells was 2-fold enhanced. Confocal laser scanning microscopy further demonstrated a higher motility of ligands in the membrane of confluent cells, together with an accumulation of these ligands in distinct areas. Both facts are suggested to be responsible for an enhanced cell adhesion observed. Finally, an increased number of large distinct metastatic foci was registered in lungs of mice after i.v. inoculation of confluent cells. The results indicate that domain organization and fluidity of the cell membrane affect tumor cell adhesion and can have in this way also an impact on the malignancy of breast cancer cells.
Zeisig
Reiner
R
Max-Delbrück Center for Molecular Medicine, Experimental Pharmacology, R-Rossle-Strasse 10, 13122 Berlin, Germany. rzeisig@mdc-berlin.de
Koklic
Tilen
T
Wiesner
Burkhard
B
Fichtner
Iduna
I
Sentjurc
Marjeta
M
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology* / Q000556:secondary*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D006801:Humans; D008560:Membrane Fluidity; D000090023:Metallothionein 3; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D013223:Statistics as Topic