Transendothelial migration of two metastatic breast carcinoma cells depend on the SDF-lalpha-CXCR4 complexes.
The role of the SDF-1alpha 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-1alpha, 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-1alpha; neutralizing anti-CXCR4 antibody inhibits the SDF-1alpha chemoattractant effect; CXCR4 expression, measured by cytofluorometry, was enhanced after treatment with SDF-1alpha on MDA-MB-231 cells but remained unchanged on MDA-MB-435 cells; Scatchard analysis evidences 8.10(5) and 2.10(5) 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-1alpha.
Lechertier
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INSERM U553, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75475 Paris 10, France.
Berard
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M
Vassy
R
R
Herve
M A
MA
Crepin
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M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism / Q000494:pharmacology*; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4