Abstract
The role of the SDF-1α chemokine-CXCR4 receptor system on tumor cell transendothelial migration was studied by culturing metastatic breast tumor cell lines, MDA-MB-231 and MDA-MB-435, either alone or on a HUVEC monolayer pre-established on a “Transwell” filter. After a 24-hour culture in the presence or absence of SDF-1α, tumor cell transmigration rates were compared. We showed that: CXCR4 is present on both cell lines; MDA-MB-231 but not MDA-MB-435 cell migration is stimulated by increasing concentrations of SDF-1α; neutralizing anti-CXCR4 antibody inhibits the SDF-1α chemoattractant effect; CXCR4 expression, measured by cytofluorometry, was enhanced after treatment with SDF-1α on MDA-MB-231 cells but remained unchanged on MDA-MB-435 cells; Scatchard analysis evidences 8.105 and 2.105 high affinity sites (KD range: 20 to 30 nM) on, respectively, MDA-MB-231 and MDA-MB-435 cells. These significant differences could explain the distinctive transendothelial migration responses of these two cell lines in the presence of SDF-1α
Footnotes
- Received April 2, 2004.
- Accepted July 2, 2004.
- Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved