Department of Biochemistry, School of Dentistry and Brain Korea 21, Kyungpook National University and ProtAnBio, Daegu, South Korea.
J Proteome Res. 2011 Mar 4;10(3):1383-95. doi: 10.1021/pr101154j. Epub 2011 Jan 25.
Lung cancer is recently regarded as an overhealed inflammatory disease. Serum amyloid A (SAA) is known as an acute phase protein, but it is likely involved in the cancer pathogenesis. We identified both SAA1 and SAA2 in the pooled sera of lung cancer patients but not in the healthy control, by LC-MS/MS analysis. We found that about 14-fold higher levels of SAA in lung cancer patients' sera and plasma compared to healthy controls by ELISA using total 350 samples (13.89 ± 37.18 vs 190.49 ± 234.70 ug/mL). The SAA levels were also significantly higher than in other pulmonary disease or other cancers. An immunohistochemical study using tissue microarray showed that, unlike other cancer tissues, lung cancer tissues highly express SAA. Further in vitro experiments showed that SAA is induced from lung cancer cells by the interaction with THP-1 monocytes and this, in return, induces MMP-9 from THP-1. In in vivo animal models, overexpressed SAA promoted Lewis lung carcinoma (LLC) cells to metastasize and colonize in the lung. Our data suggest that a higher concentration of SAA can serve as an indicator of lung adenocarcinoma and represents a therapeutic target for the inhibition of lung cancer metastasis.
肺癌最近被认为是一种过度愈合的炎症性疾病。血清淀粉样蛋白 A（SAA）是一种急性期蛋白，但它可能参与了癌症的发病机制。通过 LC-MS/MS 分析，我们在肺癌患者的混合血清中鉴定出 SAA1 和 SAA2，但在健康对照组中没有。我们发现，通过 ELISA 分析 350 例样本，肺癌患者血清和血浆中的 SAA 水平比健康对照组高约 14 倍（13.89±37.18 vs 190.49±234.70 ug/mL）。SAA 水平也明显高于其他肺部疾病或其他癌症。使用组织微阵列的免疫组织化学研究表明，与其他癌症组织不同，肺癌组织高度表达 SAA。进一步的体外实验表明，SAA 是由肺癌细胞与 THP-1 单核细胞相互作用诱导产生的，而这反过来又会诱导 THP-1 产生 MMP-9。在体内动物模型中，过表达的 SAA 促进 Lewis 肺癌（LLC）细胞转移并在肺部定植。我们的数据表明，较高浓度的 SAA 可以作为肺腺癌的指标，并代表抑制肺癌转移的治疗靶点。
