文章：

癌症和趋化因子网络

Cancer and the chemokine network

原文发布日期：2004-07-01

DOI: 10.1038/nrc1388

类型: Review Article

开放获取: 否

要点：

1. Chemokines are a subset of cytokines that cause the directed migration of leukocytes along a chemical gradient of ligand, known as the chemokine gradient. More than 50 human chemokines and 18 chemokine receptors have been discovered so far.
2. Many cancers have a complex chemokine network that influences the immune-cell infiltration of a tumour, as well as tumour cell growth, survival and migration, and angiogenesis.
3. Immune cells, endothelial cells and tumour cells themselves express chemokine receptors and can respond to chemokine gradients.
4. Chemokines are a key determinant of the macrophage and lymphocyte infiltrate of human cancers and might contribute to T-helper 2 cell polarization.
5. Malignant cells from different cancer types have different profiles of chemokine-receptor expression, but CXCR4 is most commonly found; at the last count, cells from 23 different cancer types expressed this receptor.
6. Mutations in genes that alter levels of hypoxia-inducible factor, or gene-fusion events, can induce CXCR4 in cells that do not normally express this receptor. CXCR4 is also transiently increased by factors such as hypoxia, vascular endothelial growth factor and oestrogen in the tumour microenvironment.
7. Studies of human cancer biopsy sampler and mouse cancer models show that cancer cell chemokine-receptor expression is associated with increased metastatic capacity.
8. Preliminary laboratory data show that chemokine-receptor antagonists inhibit macrophage infiltrates, can induce tumour growth arrest or apoptosis, and prevent metastatic spread.
9. Research into the cancer chemokine network is revealing parallels between the pathology of inflammation and malignancy, parallels that enhance our understanding of both types of disease and indicate new approaches for treatment.

要点翻译：

1. 趋化因子是细胞因子的一个亚类，能够引导白细胞沿着配体化学梯度（即趋化因子梯度）进行定向迁移。目前人类已发现超过50种趋化因子和18种趋化因子受体。
2. 多种癌症中存在复杂的趋化因子网络，该网络不仅影响肿瘤的免疫细胞浸润，还调控肿瘤细胞的生长、存活、迁移以及血管生成。
3. 免疫细胞、内皮细胞及肿瘤细胞自身均表达趋化因子受体，并能对趋化因子梯度作出反应。
4. 趋化因子是人类癌症中巨噬细胞和淋巴细胞浸润的关键决定因素，并可能促进辅助性T细胞2型极化。
5. 不同癌种的恶性细胞具有不同的趋化因子受体表达谱，但CXCR4是最常见的受体——最新统计显示23种不同癌症类型的细胞均表达该受体。
6. 改变缺氧诱导因子水平的基因突变或基因融合事件，可诱导原本不表达CXCR4的细胞产生该受体。肿瘤微环境中的缺氧、血管内皮生长因子和雌激素等因素也会短暂上调CXCR4表达。
7. 对人类癌症活检样本及小鼠癌症模型的研究表明，癌细胞趋化因子受体的表达与转移能力增强相关。
8. 初步实验室数据显示，趋化因子受体拮抗剂不仅能抑制巨噬细胞浸润，还能诱导肿瘤生长停滞或细胞凋亡，并阻止转移扩散。
9. 对癌症趋化因子网络的研究揭示了炎症与恶性肿瘤病理过程的相似性，这种相似性深化了我们对两类疾病的理解，并为治疗策略开发指明了新方向。

英文摘要：

A complex network of chemokines and their receptors influences the development of primary tumours and metastases. New information about the biological role of chemokines in these processes is providing insights into host–tumour interactions, such as the role of the leukocyte infiltrate, and into the mechanisms that determine the metastatic potential and site-specific spread of cancer cells. Chemokine-receptor antagonists are showing promise in animal models of inflammation and autoimmune disease. Could manipulating the local chemokine network have therapeutic benefits in malignant disease?

摘要翻译： 

一个复杂的趋化因子及其受体网络影响着原发肿瘤和转移灶的发展。关于趋化因子在这些过程中生物学作用的新信息，为了解宿主与肿瘤之间的相互作用（如白细胞浸润的作用）以及决定癌细胞转移潜能和特定部位扩散的机制提供了洞见。趋化因子受体拮抗剂在炎症和自身免疫性疾病的动物模型中显示出前景。调控局部趋化因子网络是否能在恶性疾病中带来治疗益处？

原文链接：

Cancer and the chemokine network