Lechertier T, Berard M, Vassy R, Herve M A, Crepin M
INSERM U553, Hôpital Saint Louis, 1 Avenue Claude Vellefaux, 75475 Paris 10, France.
Anticancer Res. 2004 Nov-Dec;24(6):4011-7.
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.
通过培养转移性乳腺癌细胞系MDA-MB-231和MDA-MB-435（单独培养或培养于预先在“Transwell”滤膜上建立的人脐静脉内皮细胞（HUVEC）单层上），研究了基质细胞衍生因子-1α（SDF-1α）趋化因子-CXCR4受体系统在肿瘤细胞跨内皮迁移中的作用。在有或无SDF-1α存在的情况下进行24小时培养后，比较肿瘤细胞的迁移率。我们发现：两种细胞系均存在CXCR4；SDF-1α浓度增加可刺激MDA-MB-231细胞迁移，但不刺激MDA-MB-435细胞迁移；中和性抗CXCR4抗体可抑制SDF-1α的趋化作用；通过细胞荧光测定法检测，用SDF-1α处理后，MDA-MB-231细胞上的CXCR4表达增强，但MDA-MB-435细胞上的CXCR4表达保持不变；Scatchard分析表明，MDA-MB-231和MDA-MB-435细胞上分别有8×10⁵和2×10⁵个高亲和力位点（解离常数（KD）范围：20至30 nM）。这些显著差异可以解释这两种细胞系在SDF-1α存在时不同的跨内皮迁移反应。
