Plasma Shh levels reduced in pancreatic cancer patients.
Plasma Shh levels reduced in pancreatic cancer patients.
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DOI：
10.1097/mpa.0b013e31824a0eeb
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发表时间：
2012-10
期刊：
影响因子：
2.9
通讯作者：
Merchant JL
中科院分区：
文献类型：
--
作者：
El-Zaatari M;Daignault S;Tessier A;Kelsey G;Travnikar LA;Cantu EF;Lee J;Plonka CM;Simeone DM;Anderson MA;Merchant JL
正常情况下，Sonic Hedgehog(Shh)在胎儿发育期间和组织损伤后短暂地在胰腺中表达。虽然胰腺癌表达Shh，但尚不清楚Shh蛋白是否分泌到血液中，以及其血浆水平是否随着胰腺癌的转变而变化。这项研究的目的是建立一种检测血液中人类Shh的酶联免疫吸附试验，并确定患有和不患有胰腺癌的受试者的Shh水平。建立了人Shh-EL ISA方法，并测定了正常志愿者和胰腺炎或胰腺癌患者的血浆Shh水平。用NIH-3T3细胞检测血浆Shh的生物学活性。胰腺炎和胰腺癌患者血液中Shh的平均水平低于正常人。造血细胞不表达Shh，提示Shh被分泌到血液中。富含Shh的血浆组分不能诱导Gli-1mRNA，这表明该蛋白没有生物活性。Shh从组织和器官分泌到循环中，但其活性被血浆蛋白阻止。在胰腺癌患者中发现血浆水平降低，但仅凭血浆水平不足以预测胰腺癌。
Normally, sonic hedgehog (Shh) is expressed in the pancreas during fetal development and transiently after tissue injury. Although pancreatic cancers express Shh, it is not known if the protein is secreted into the blood and whether its plasma levels change with pancreatic transformation. The goal of this study was to develop an ELISA to detect human Shh in blood, and determine the levels in subjects with and without pancreatic cancer. A human Shh ELISA assay was developed, and plasma Shh levels were measured in blood samples from normal volunteers and subjects with pancreatitis or pancreatic cancer. The biological activity of plasma Shh was tested using NIH-3T3 cells. The average levels of Shh in human blood were lower in pancreatitis and pancreatic cancer patients than in normal individuals. Hematopoietic cells did not express Shh suggesting that Shh is secreted into the bloodstream. Plasma fractions enriched for Shh did not induce Gli-1 mRNA suggesting that the protein was not biologically active. Shh is secreted from tissues and organs into the circulation but its activity is blocked by plasma proteins. Reduced plasma levels were found in pancreatic cancer patients, but alone were not sufficient to predict pancreatic cancer.