Pellegrino Antonio, Vacca Angelo, Scavelli Claudio, Dammacco Franco
Dipartimento di Scienze Biomediche e Oncologia Umana, Università, Bari.
Recenti Prog Med. 2002 Nov;93(11):642-54.
Chemokines are cytokines which induce chemotaxis on many cell types, thus regulating cell migration within inflammatory and allergic sites, and leucocyte homing. Also, they play a crucial role in inflammatory and tumor-associated angiogenesis, as well as in tumor progression. Chemokines are grouped into: 1) alpha or CXC; 2) beta or CC; 3) gamma or C; 4) delta or CX3C molecules. Each of them recognizes one or more cell surface receptors, named CXCR, CCR, XCR, CX3CR respectively, according to the corresponding subfamily. Many chemokines have been identified within tumor tissues, as a secretory product of tumor cells and/or inflammatory cells. The CXC chemokines (such as IL-8, IP10, Mig, SDF-1 alpha) or CC chemokines (such as MCP-1, MIP-1 alpha, eotaxin, RANTES) have been frequently harvested from tumor tissues or the biological fluids of patients. Some chemokines inhibit tumor growth and progression by activating immunocompetent cytolytic cells or inhibiting tumor-associated angiogenesis. In contrast, other chemokines induce tumor progression by interacting with the specific receptor expressed on the tumor cells and hence by activating chemotaxis and secretion of proteolytic enzymes, or by inducing angiogenesis and metastatic spreading. Sometimes neoplastic cells express chemokine receptors which are not expressed on their normal counterpart. Data from this lab show the CXCR3 expression by cells from lymphoproliferative diseases, such as multiple myeloma and lymphoma, and the stimulation of an invasive phenotype following interaction with specific chemokines.
趋化因子是一类细胞因子,可诱导多种细胞类型发生趋化作用,从而调节炎症和过敏部位的细胞迁移以及白细胞归巢。此外,它们在炎症和肿瘤相关的血管生成以及肿瘤进展中也起着关键作用。趋化因子可分为:1)α或CXC;2)β或CC;3)γ或C;4)δ或CX3C分子。它们各自识别一种或多种细胞表面受体,根据相应亚家族分别命名为CXCR、CCR、XCR、CX3CR。在肿瘤组织中已鉴定出许多趋化因子,它们是肿瘤细胞和/或炎症细胞的分泌产物。CXC趋化因子(如IL-8、IP10、Mig、SDF-1α)或CC趋化因子(如MCP-1、MIP-1α、嗜酸性粒细胞趋化因子、RANTES)经常从肿瘤组织或患者的生物体液中获取。一些趋化因子通过激活免疫活性溶细胞或抑制肿瘤相关血管生成来抑制肿瘤生长和进展。相反,其他趋化因子通过与肿瘤细胞上表达的特定受体相互作用,从而激活趋化作用和蛋白水解酶的分泌,或通过诱导血管生成和转移扩散来诱导肿瘤进展。有时肿瘤细胞表达其正常对应细胞所不表达的趋化因子受体。本实验室的数据显示,来自淋巴增殖性疾病(如多发性骨髓瘤和淋巴瘤)的细胞表达CXCR3,并且在与特定趋化因子相互作用后刺激侵袭性表型。