Hisamatsu Eriko, Nagao Manabu, Toh Ryuji, Irino Yasuhiro, Iino Takuya, Hara Tetsuya, Tanaka Hidekazu, Satomi-Kobayashi Seimi, Ishida Tatsuro, Hirata Ken-Ichi
Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Division of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Kobe J Med Sci. 2020 Aug 17;66(1):E40-E48.
A large amount of evidence suggests that high-density lipoprotein (HDL) has anti-atherosclerotic properties. HDL-cholesterol (HDL-C) has also been widely used as a marker of cardiovascular disease. Recently, it was reported that plasma HDL-C levels are inversely correlated with cancer risk. However, the relationship between HDL and cancer pathophysiology remains unknown. Here, we sought to investigate the effect of HDL on cancer progression. First, we focused on fibronectin-an essential extracellular matrix glycoprotein-as an HDL-associated protein and found that only 7.4% of subjects in this study had fibronectin in HDL isolated from their plasma. The fibronectin-containing HDL (FN-HDL) increased the phosphorylation of focal adhesion kinase (FAK) in HeLa cells compared to HDL without fibronectin, further inducing the phosphorylation in a dose-dependent manner. Second, we found that fibronectin-treated HDL activated the phosphorylation of FAK, and its upstream effector blocked the phosphorylation induced by FN-HDL. Finally, we demonstrated that FN-HDL promoted cancer cell proliferation and adhesion compared to HDL without fibronectin. Our study showed the possible mechanism by which FN-HDL enhanced cancer cell proliferation and adhesion via the FAK signaling pathway. Further investigation of the roles of HDL components in tumorigenesis might provide novel insight into cancer pathophysiology.
大量证据表明高密度脂蛋白（HDL）具有抗动脉粥样硬化特性。HDL胆固醇（HDL-C）也已被广泛用作心血管疾病的标志物。最近，有报道称血浆HDL-C水平与癌症风险呈负相关。然而，HDL与癌症病理生理学之间的关系仍不清楚。在此，我们试图研究HDL对癌症进展的影响。首先，我们聚焦于纤连蛋白——一种重要的细胞外基质糖蛋白——作为与HDL相关的蛋白，发现本研究中只有7.4%的受试者血浆分离出的HDL中含有纤连蛋白。与不含纤连蛋白的HDL相比，含纤连蛋白的HDL（FN-HDL）增加了HeLa细胞中粘着斑激酶（FAK）的磷酸化，并进一步以剂量依赖方式诱导磷酸化。其次，我们发现纤连蛋白处理的HDL激活了FAK的磷酸化，其上游效应器阻断了FN-HDL诱导的磷酸化。最后，我们证明与不含纤连蛋白的HDL相比，FN-HDL促进了癌细胞的增殖和粘附。我们的研究揭示了FN-HDL通过FAK信号通路增强癌细胞增殖和粘附的可能机制。进一步研究HDL成分在肿瘤发生中的作用可能会为癌症病理生理学提供新的见解。
