趨化因子是能使細(xì)胞發(fā)生趨化運(yùn)動(dòng)的小分子細(xì)胞因子,，分子量多在8-14kDa之間,。趨化因子與趨化因子受體結(jié)合后傳遞多種細(xì)胞信息,。CXCL5是一個(gè)小分子類型的分泌蛋白，屬于趨型趨化因子家族成員,。近來，CXCL5與癌癥發(fā)生發(fā)展的相關(guān)證據(jù)已經(jīng)有很多,。
最近,，為了研究CXCL5在肝細(xì)胞癌的生長(zhǎng)、侵襲和預(yù)后中的作用,，研究人員研究了具有不同轉(zhuǎn)移性能的人肝癌細(xì)胞系以及919例肝癌患者中CXCL5的mRNA和蛋白水平,。
結(jié)果發(fā)現(xiàn)在高轉(zhuǎn)移人肝癌細(xì)胞系中，CXCL5表達(dá)水平增加,，與對(duì)照組相比,，復(fù)發(fā)性肝癌患者的腫瘤組織中，CXCL5表達(dá)水平也增加,。
CXCL5 激活肝癌細(xì)胞的PI3K-AKT和ERK1/2信號(hào)通路,，促進(jìn)腫瘤增殖、遷移和侵襲,。此外,，在體外研究中，CXCL5對(duì)中性粒細(xì)胞有直接趨化作用,。在動(dòng)物實(shí)驗(yàn)中,，肝癌細(xì)胞中CXCL5的上調(diào)促進(jìn)腫瘤細(xì)胞的生長(zhǎng)以及肺轉(zhuǎn)移，瘤內(nèi)中性粒細(xì)胞浸潤(rùn)數(shù)目也增加,。
相反,，肝癌細(xì)胞的CXCL5表達(dá)被下調(diào)后，腫瘤生長(zhǎng)被抑制,，肺轉(zhuǎn)移和腫瘤組織中性粒細(xì)胞浸潤(rùn)數(shù)量都減少,。肝癌樣本中免疫組化分析表明，瘤組織中CXCL5的過度表達(dá)與中性粒細(xì)胞的浸潤(rùn),、患者總生存期短以及腫瘤患者的復(fù)發(fā)相關(guān),。多變量分析顯示，CXCL5過表達(dá)或與瘤內(nèi)中性粒細(xì)胞同時(shí)存在,，都是一個(gè)獨(dú)立的整體生存和癌癥復(fù)發(fā)預(yù)后指標(biāo),。該研究的結(jié)論就是CXCL5促進(jìn)肝癌細(xì)胞增殖、侵襲,，促進(jìn)瘤內(nèi)中性粒細(xì)胞的浸潤(rùn),。（生物谷：Bioon.com）
doi:10.1002/hep.25907
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PMID:
Overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma.
Zhou SL, Dai Z, Zhou ZJ, Wang XY, Yang GH, Wang Z, Huang XW, Fan J, Zhou J.
CXCL5 (epithelial neutrophil-activating peptide-78) is a member of a proangiogenic subgroup of the CXC-type chemokine family of small, secreted proteins. Recently, evidence that CXCL5 is involved in carcinogenesis and cancer progression has emerged. To investigate the role of CXCL5 in tumor growth, invasion, and prognosis of hepatocellular carcinoma (HCC), we examined CXCL5 mRNA and protein levels in HCC cell lines with various metastatic potentials and in three independent cohorts of 919 HCC patients. We found that CXCL5 expression was increased in the highly metastatic HCC cell lines and in tumor tissues from patients with recurrent HCC compared to controls. CXCL5 activated the PI3K-Akt and ERK1/2 signaling pathways in HCC cells and promoted proliferation, migration, and invasion. Furthermore, we found that CXCL5 had a direct chemoattractant effect on neutrophils in vitro. In animal studies, the up-regulation of CXCL5 in HCC cells promoted tumor growth, lung metastasis, and intratumoral neutrophil infiltration. Conversely, down-regulation of CXCL5 in HCC cells reduced tumor growth, metastasis, and intratumoral neutrophil infiltration. Immunohistochemical analysis in HCC samples showed that overexpression of CXCL5 was well correlated with intratumoral neutrophil infiltration, shorter overall survival, and tumor recurrence. Multivariate analysis revealed that CXCL5 overexpression alone, or combined with the presence of intratumoral neutrophils, was an independent prognostic indicator for overall survival and cumulative recurrence. CONCLUSION: CXCL5 promotes HCC cell proliferation, invasion, and intratumoral neutrophil infiltration. CXCL5 overexpression, alone or combined with intratumoral neutrophil presence, is a novel prognostic predictor, and CXCL5 is a potential therapeutic target for HCC. (HEPATOLOGY 2012.).
