音猬因子促进胰腺癌的促结缔组织增生反应。
Sonic hedgehog promotes desmoplasia in pancreatic cancer.
作者信息
Bailey Jennifer M, Swanson Benjamin J, Hamada Tomofumi, Eggers John P, Singh Pankaj K, Caffery Thomas, Ouellette Michel M, Hollingsworth Michael A
机构信息
Eppley Institute, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198, USA.
出版信息
Clin Cancer Res. 2008 Oct 1;14(19):5995-6004. doi: 10.1158/1078-0432.CCR-08-0291.
PURPOSE
We investigated the contribution of Sonic hedgehog (SHH) to pancreatic cancer progression.
EXPERIMENTAL DESIGN
We expressed SHH in a transformed primary ductal-derived epithelial cell line from the human pancreas, transformed hTert-HPNE (T-HPNE), and evaluated the effects on tumor growth. We also directly inhibited the activity of SHH in vivo by administering a blocking antibody to mice challenged orthotopically with the Capan-2 pancreatic cancer cell line, which is known to express SHH and form moderately differentiated tumors in nude mice.
RESULTS
Our data provide evidence that expression of SHH influences tumor growth by contributing to the formation of desmoplasia in pancreatic cancer. We further show that SHH affects the differentiation and motility of human pancreatic stellate cells and fibroblasts.
CONCLUSIONS
These data suggest that SHH contributes to the formation of desmoplasia in pancreatic cancer, an important component of the tumor microenvironment.
目的
我们研究了音猬因子（SHH）对胰腺癌进展的作用。
实验设计
我们在源自人胰腺的转化原发性导管上皮细胞系——转化的hTert-HPNE（T-HPNE）中表达SHH，并评估其对肿瘤生长的影响。我们还通过向原位接种已知表达SHH并在裸鼠中形成中度分化肿瘤的Capan-2胰腺癌细胞系的小鼠施用阻断抗体，在体内直接抑制SHH的活性。
结果
我们的数据提供了证据，表明SHH的表达通过促进胰腺癌中促结缔组织增生的形成来影响肿瘤生长。我们进一步表明，SHH影响人胰腺星状细胞和成纤维细胞的分化和运动。
结论
这些数据表明，SHH有助于胰腺癌中促结缔组织增生的形成，这是肿瘤微环境的一个重要组成部分。
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