Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate.

Distinct expression pattern of the full set of secreted phospholipases A2 in human colorectal adenocarcinomas: sPLA2-III as a biomarker candidate.
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人类结直肠腺癌中的全部分泌磷脂酶A2的全部表达模式:SPLA2-III作为生物标志物候选者。

DOI:
10.1038/sj.bjc.6604184
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发表时间:
2008-02-12
影响因子:
8.8
通讯作者:
Lambeau, G.
Lambeau, G.
中科院分区:
医学1区
文献类型:
--
作者:
Mounier, C. M.;Wendum, D.;Greenspan, E.;Flejou, J. -F;Rosenberg, D. W.;Lambeau, G.

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最近的研究表明,分泌型磷脂酶A2(sPLA 2)代表有吸引力的潜在的肿瘤生物标志物和各种癌症的治疗靶点。作为第一步,以解决这个问题,在人类结直肠癌,我们研究了一套完整的sPLA 2的表达在散发性腺癌和正常匹配的粘膜从21例患者通过定量PCR和免疫组化。在正常结肠组织中,PLA 2G 2A和PLA 2G 12 A高水平表达,PLA 2G 2D、PLA 2G 5、PLA 2G 10和PLA 2G 12 B中等水平表达,PLA 2G 1B、PLA 2G 2F和PLA 2G 3低水平表达。在左右结肠腺癌中,PLA 2G 3的表达增加了40倍,而PLA 2G 2D和PLA 2G 5的表达降低了23倍和14倍。在蛋白水平上证实了sPLA 2-IID、sPLA 2-III和sPLA 2-V的表达变化。这些sPLA 2的表达模式似乎分别与IL-8、防御素α6、生存素和基质溶解素的过表达以及SFRP-1和RLPA-1的下调有关,所有这些基因都与结肠癌相关。在腺癌中观察到的这种原始sPLA 2谱突出了某些sPLA 2在结肠癌中的潜在作用,并表明sPLA 2-III可能是作为左结肠癌和右结肠癌的新型生物标志物的良好候选者。
Recent studies suggest that secreted phospholipases A2 (sPLA2s) represent attractive potential tumour biomarkers and therapeutic targets for various cancers. As a first step to address this issue in human colorectal cancer, we examined the expression of the full set of sPLA2s in sporadic adenocarcinomas and normal matched mucosa from 21 patients by quantitative PCR and immunohistochemistry. In normal colon, PLA2G2A and PLA2G12A were expressed at high levels, PLA2G2D, PLA2G5, PLA2G10 and PLA2G12B at moderate levels, and PLA2G1B, PLA2G2F and PLA2G3 at low levels. In adenocarcinomas from left and right colon, the expression of PLA2G3 was increased by up to 40-fold, while that of PLA2G2D and PLA2G5 was decreased by up to 23- and 14-fold. The variations of expression for sPLA2-IID, sPLA2-III and sPLA2-V were confirmed at the protein level. The expression pattern of these sPLA2s appeared to be linked respectively to the overexpression of interleukin-8, defensin α6, survivin and matrilysin, and downregulation of SFRP-1 and RLPA-1, all these genes being associated to colon cancer. This original sPLA2 profile observed in adenocarcinomas highlights the potential role of certain sPLA2s in colon cancer and suggests that sPLA2-III might be a good candidate as a novel biomarker for both left and right colon cancers.
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