Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels during carcinogenic process in human colorectal tract.
Progressive increase of matrix metalloprotease-9 and interleukin-8 serum levels during carcinogenic process in human colorectal tract.
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DOI：
10.1371/journal.pone.0041839
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Poli G
中科院分区：
文献类型：
--
作者：
Biasi F;Guina T;Maina M;Nano M;Falcone A;Aroasio E;Saracco GM;Papotti M;Leonarduzzi G;Poli G
已知促进肿瘤生长和侵袭的炎症反应与结直肠癌（CRC）相关。巨噬细胞是炎症浸润的主要成分，其发生在从非侵袭性肿瘤到恶性肿瘤的进展的早期，具有从促炎表型到肿瘤促进表型的转变。肿瘤和间质是炎症相关分子的额外来源。本研究旨在评估结直肠癌从良性到恶性的发展过程中：i）血清IL-8、IL-6、TGFβ1、VEGF和MMPs水平的变化趋势; ii）血清CRP水平的平行变化趋势; iii）肿瘤组织中主要TGFβ1受体（TGFβ 1 RI/RII）的紊乱。招募了96名处于不同进展阶段的结肠腺瘤或CRC患者和17名对照。分别于内镜检查前和手术前检测血清IL-8、IL-6、TGFβ1、VEGF、MMPs和CRP水平。在腺瘤活检和切除的结直肠腺癌中评估TGFβ1受体。腺癌患者的血清IL-8水平从II期开始升高，此时MMP-9的酶活性也升高。值得注意的是，发现两种血清标志物的增加趋势显著相关。血清CRP的变化趋势与IL-8和MMP-9的变化趋势也非常相似，但略低于统计学意义。III期CRC患者TGFβ1水平较低，而IL-6和VEGF水平无显著变化。在组织标本中，大约50%的腺瘤中已经缺乏TGFβ1受体，并且在CRC III期和IV期中缺失受体的百分比显著增加。血清IL-8、MMP-9和CRP的组合定量似乎是结直肠癌发生的恶性阶段期间炎症相关过程的可靠和先进的指标，因为这些分子在携带结直肠腺瘤的患者中保持在正常范围内，而在CRC患者的血液中持续增加，即使仅从II期开始。
Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC). Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i) the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii) the parallel trend of CRP serum levels; iii) derangement of the principal TGFβ1 receptors (TGFβ1RI/RII) in tumor tissues. 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV. Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in the blood of CRC patients, even if from stage II only.
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