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首页> 外文期刊>Cell and Tissue Research >Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells
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Effects of the chemokine CXCL12 and combined internalization of its receptors CXCR4 and CXCR7 in human MCF-7 breast cancer cells

机译：趋化因子CXCL12及其受体CXCR4和CXCR7的组合内在作用在人MCF-7乳腺癌细胞中的作用

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摘要

The chemokine CXCL12 (stromal cell-derived factor-1, SDF-1) and its receptor CXCR4 play a major role in tumor initiation, promotion, progression and metastasis, especially for breast cancer cells. Recently, CXCR7 has been identified as a second receptor for CXCL12; nevertheless, it also binds CXCL11 (interferon-inducible T cell α chemoattractant, I-TAC). However, little is known about the co-expression of the two receptors and their interactions. Quantitative reverse transcription plus the polymerase chain reaction has demonstrated that both receptors are frequently co-expressed in breast cancer cell lines, whereas other tumor cell lines often express only one of them. For interaction studies, we chose MCF-7 breast cancer cells, since they highly express CXCR4 and CXCR7 at the protein level but not CXCR3 (another target for CXCL11). Immunofluorescence and gold-labeling by light and electron microscopy, respectively, revealed that both receptors were localized at the cell surface in non-stimulated cells. After exposure to CXCL12 or CXCL11, the receptors were rapidly internalized alone or in close proximity. Stimulation with the CXCR4- or CXCR7-selective non-peptide antagonists AMD3100 and CCX733 resulted not only in single internalization but partly also in co-internalization of the two receptors. Furthermore, both chemokine ligands reduced staurosporine-induced apoptosis and caspase-3/7 activation; however, the selective inhibitors merely had partial inhibitory effects on these biological responses. Our findings suggest that CXCR4 and CXCR7 closely interact in breast cancer cells. Both are co-internalized, transduce signals and induce further biological effects partly independently of a selective stimulus or antagonist.
机译：趋化因子CXCL12（基质细胞衍生因子-1，SDF-1）及其受体CXCR4在肿瘤的发生，促进，发展和转移中起着重要作用，尤其是对于乳腺癌细胞。最近，CXCR7被确定为CXCL12的第二受体。但是，它也结合CXCL11（干扰素诱导性T细胞α化学引诱剂I-TAC）。然而，关于两种受体的共表达及其相互作用知之甚少。定量逆转录加上聚合酶链反应已证明，这两种受体在乳腺癌细胞系中经常共表达，而其他肿瘤细胞系通常仅表达其中一种。对于相互作用研究，我们选择MCF-7乳腺癌细胞，因为它们在蛋白水平上高表达CXCR4和CXCR7，但不表达CXCR3（CXCL11的另一个靶标）。分别通过光镜和电子显微镜进行的免疫荧光和金标记表明，这两种受体均位于非刺激细胞的细胞表面。暴露于CXCL12或CXCL11后，受体被迅速内在化，成为单独或紧密结合的形式。用CXCR4或CXCR7选择性非肽拮抗剂AMD3100和CCX733刺激不仅导致单个内在化，而且部分导致两个受体的共内在化。此外，两种趋化因子配体均减少了星形孢菌素诱导的细胞凋亡和caspase-3 / 7活化。然而，选择性抑制剂仅对这些生物学反应具有部分抑制作用。我们的发现表明CXCR4和CXCR7在乳腺癌细胞中紧密相互作用。两者都是共同内在化的，转导信号并部分地独立于选择性刺激或拮抗剂而引起进一步的生物学作用。

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