Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo
Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo
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DOI：
10.4049/jimmunol.174.9.5490
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发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Shurin, MR
中科院分区：
文献类型：
--
作者：
Shurin, GV;Ferris, R;Shurin, MR
Breast and kidney expression chemokine (BRAK) CXCL14是一种新的CXC趋化因子，其功能和受体选择性尚不清楚。大多数头颈部鳞状细胞癌（HNSCC）和部分宫颈鳞状细胞癌不表达CXCL14 mRNA，与正常口腔鳞状上皮的组成性表达相反。在这项研究中，我们证明了CXCL14在HNSCC细胞和HNSCC原发肿瘤部位的缺失与体外树突状细胞（DC）的低吸引力或无吸引力以及体内DC在肿瘤部位浸润HNSCC肿块的减少有关。接下来，我们发现重组人CXCL14和CXCL14阳性HNSCC细胞系在体外诱导DC吸引，而CXCL14阴性HNSCC细胞没有化学吸引DC。在嵌合动物模型中，用人CXCL14基因转导CXCL14阴性HNSCC细胞系，在体外刺激DC吸引，并增加DC在体内的肿瘤浸润。此外，通过评估CXCL14对DC的生物学效应，我们发现在DC培养物中加入重组人CXCL14可上调DC成熟标志物的表达，并增强MLR中异体T细胞的增殖。重组人CXCL14对DC的激活伴随着nf - κ B活性的上调。这些数据表明，CXCL14是一种有效的DC化学引诱剂和激活剂，可能参与DC在体内的归巢。
Breast and kidney-expressed chemokine (BRAK) CXCL14 is a new CXC chemokine with unknown function and receptor selectivity. The majority of head and neck squamous cell carcinoma (HNSCC) and some cervical squamous cell carcinoma do not express CXCL14 mRNA, as opposed to constitutive expression by normal oral squamous epithelium. In this study, we demonstrate that the loss of CXCL14 in HNSCC cells and at HNSCC primary tumor sites was correlated with low or no attraction of dendritic cell (DC) in vitro, and decreased infiltration of HNSCC mass by DC at the tumor site in vivo. Next, we found that recombinant human CXCL14 and CXCL14-positive HNSCC cell lines induced DC attraction in vitro, whereas CXCL14-negative HNSCC cells did not chemoattract DC. Transduction of CXCL14-negative HNSCC cell lines with the human CXCL14 gene resulted in stimulation of DC attraction in vitro and increased tumor infiltration by DC in vivo in chimeric animal models. Furthermore, evaluating the biologic effect of CXCL14 on DC, we demonstrated that the addition of recombinant human CXCL14 to DC cultures resulted in up-regulation of the expression of DC maturation markers, as well as enhanced proliferation of allogeneic T cells in MLR. Activation of DC with recombinant human CXCL14 was accompanied by up-regulation of NF-kappa B activity. These data suggest that CXCL14 is a potent chemoattractant and activator of DC and might be involved in DC homing in vivo.