The role of the CCL22-CCR4 axis in the metastasis of gastric cancer cells into omental milky spots.
The role of the CCL22-CCR4 axis in the metastasis of gastric cancer cells into omental milky spots.
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CCL22-CCR4轴在胃癌细胞大网膜乳斑转移中的作用
DOI：
10.1186/s12967-014-0267-1
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发表时间：
2014-09-24
影响因子：
7.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Cao L;Hu X;Zhang J;Huang G;Zhang Y
背景网膜是腹膜转移的起始部位之一，因为它具有乳斑，为癌细胞容易迁移和生长成微转移提供了微环境。本研究探讨了CCL 22-CCR 4轴在胃癌细胞选择性浸润乳斑中的作用。以指定的时间间隔对小鼠实施安乐死，并切除大网膜进行免疫组织化学。MTT法和trans-well法检测CCL 22对MFC增殖和迁移的影响。RT-PCR和Western blot检测微囊细胞中CCR 4 mRNA和蛋白的表达水平。免疫组化法检测乳斑微转移灶中CCL 22和CCR 4的表达。结果腹腔注射后2周，乳斑区完全被增殖的胃癌细胞所占据，并可见细胞簇型微转移灶。相反，癌细胞在非乳斑区域形成单细胞型微转移。MFC表达CCR 4，其定位于细胞表面和/或细胞质中。不同浓度的CCL 22均能显著提高MFC的增殖能力。此外，浓度在10-100 ng/ml之间的CCL 22显著增加MFC的迁移。在网膜乳斑内，CCL 22主要定位于细胞表面和/或细胞质中。在网膜乳斑微转移灶的切片中，CCR 4被识别在胃癌细胞、组成细胞乳斑、血细胞和血内皮细胞上或中。CCL 22-CCR 4轴有助于这种选择性渗透过程。
BackgroundThe omentum is one of the initial sites for peritoneal metastasis because it possesses milky spots that provide a microenvironment for cancer cells to readily migrate and grow into micrometastases. This study investigated the role of the CCL22-CCR4 axis in gastric cancer cells selectively infiltrating into milky spots.MethodsGastric cancer MFC cells labelled with DiI were injected intraperitoneally into strain 615 mice. The mice were euthanised at specified intervals and the omentum was excised for immunohistochemistry. The effects of CCL22 on the proliferation and migration of MFCs were assessed by MTT and trans-well assays. RT-PCR and Western blot analysis detected CCR4 mRNA and protein expression levels in MFCs. Immunohistochemistry was used to analyse CCL22 and CCR4 expression in the milky spot micrometastases.ResultsTwo weeks after intraperitoneal injection, the milky spot areas were completely occupied by proliferating gastric cancer cells and cell cluster-type micrometastases were observed. In contrast, cancer cells formed single cell-type micrometastases in the non-milky spot areas. MFCs expressed CCR4, which was localised on the cell surface and or in the cytoplasm. Different concentrations of CCL22 significantly increased the proliferation ability of MFCs. Additionally, concentrations of CCL22 between 10–100 ng/ml significantly increased the migration of MFCs. Within omental milky spots, CCL22 was localised mainly on the cell surface and or in the cytoplasm. Within sections of omental milky spot micrometastases, CCR4 was recognised on or in gastric cancer cells, constituent cells milky spots, blood cells and blood endothelial cells.ConclusionsOmental milky spots are a congenial microenvironment for peritoneal free gastric cancer cells to migrate, survive, and establish cell cluster-type metastases. The CCL22-CCR4 axis contributes to this selective infiltration process.
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影响因子：
9.7
作者：
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通讯作者：
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