Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.
Molecular Medicine Partnetship Unit (DKFZ), Im Neuenheimer Feld 350, D-69120, Heidelberg, Germany.
Biochem Biophys Res Commun. 2018 Jun 7;500(3):731-737. doi: 10.1016/j.bbrc.2018.04.144. Epub 2018 Apr 23.
CXCL8 belongs to proinflammatory chemokines that are predominantly involved in neutrophil chemotaxis and degranulation. Several studies have suggested that secretion of CXCL8 from cancer cells have a profound effect on tumor microenvironment. In this study, in continuation to our previous work of understanding the global picture of invasion related genes in colorectal liver metastases, we clearly show an up-regulation of CXCL8 expression in the tumor cells at the invasion front as compared to the tumor cells in the inner parts of the tumor. Furthermore, ShRNA mediated down-regulation of CXCL8 resulted in inhibition of cell proliferation, viability and invasion in vitro and a near complete growth reduction of tumor in vivo. We showed that CXCL8 secreted by tumor cells at the invasion front were able to promote migration through angiogenesis by upregulating VEGFA and invasion via the AKT/GSK3β/β-catenin/MMP7 pathway by upregulating BCL-2 confirming the key role of CXCL8 during tumor progression.
CXCL8 属于前炎性趋化因子，主要参与中性粒细胞的趋化作用和脱颗粒。多项研究表明，癌细胞分泌的 CXCL8 对肿瘤微环境有深远的影响。在本研究中，在我们之前研究结直肠癌肝转移侵袭相关基因的基础上，我们清楚地显示出肿瘤细胞在侵袭前沿的 CXCL8 表达上调，与肿瘤内部的肿瘤细胞相比。此外，ShRNA 介导的 CXCL8 下调导致体外细胞增殖、活力和侵袭的抑制，以及体内肿瘤生长的几乎完全减少。我们表明，肿瘤细胞在侵袭前沿分泌的 CXCL8 通过上调 VEGFA 促进迁移，通过 AKT/GSK3β/β-catenin/MMP7 途径上调 BCL-2 促进侵袭，从而证实了 CXCL8 在肿瘤进展过程中的关键作用。
