Establishing a murine pancreatic cancer CaSm model: up-regulation of CaSm is required for the transformed phenotype of murine pancreatic adenocarcinoma.
Establishing a murine pancreatic cancer CaSm model: up-regulation of CaSm is required for the transformed phenotype of murine pancreatic adenocarcinoma.
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DOI：
10.1016/j.ymthe.2004.09.023
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发表时间：
2005-03
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影响因子：
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通讯作者：
Yan Yan-Yan;S. Rubinchik;P. Watson;J. Kelley;M. M. Fraser-M.;April L Wood;Jian-yun Dong;W. Gillanders;A. Boylan;D. Watson;D. Cole
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文献类型：
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作者：
Yan Yan-Yan;S. Rubinchik;P. Watson;J. Kelley;M. M. Fraser-M.;April L Wood;Jian-yun Dong;W. Gillanders;A. Boylan;D. Watson;D. Cole
我们最近发现，癌症相关的Sm样蛋白（CaSm）在人胰腺癌（PC）中过表达。然而，CaSm在肿瘤转化过程中的作用仍不清楚。为了进一步确定CaSm在PC转化中的作用，我们建立了基于小鼠胰腺癌细胞系Panc02和Panc03的小鼠模型。CaSm在侵袭性Panc02细胞中过表达，而在更惰性的Panc03细胞中以低得多的水平表达。上调Panc03细胞中CaSm的表达可促进Panc03细胞的体外增殖和非贴壁依赖性生长，并促进同系小鼠皮下肿瘤的建立和生长。相反，腺病毒下调Panc02中的CaSm导致体外细胞增殖和锚定非依赖性生长的显著抑制，以及体内肿瘤生长和转移的完全消除。CaSm在NIH3T3细胞中的表达上调导致细胞接触抑制作用的丧失，并使软琼脂集落形成增加。肿瘤转化需要CaSm过表达，这证实了CaSm是一个关键的癌基因和潜在的分子干预靶点的概念。此外，胰腺转移的小鼠临床相关模型的建立为临床前数据的产生提供了框架，以支持靶向CaSm的新型分子疗法的开发。
We have recently shown that the cancer-associated Sm-like protein (CaSm) is overexpressed in human pancreatic adenocarcinoma (PC). However, the role of CaSm in the process of neoplastic transformation remains unclear. To define further the role of CaSm in PC transformation, we have established a murine model based on the murine pancreatic cancer cell lines Panc02 and Panc03. CaSm is overexpressed in the aggressive Panc02 cells and expressed at much lower levels in the more indolent Panc03 cells. Up-regulation of CaSm in Panc03 cells increasedin vitroproliferation and anchorage-independent growth and promoted subcutaneous tumor establishment and growth in syngeneic mice. Conversely, adenoviral down-regulation of CaSm in Panc02 led to significant inhibition of cellular proliferation and anchorage-independent growthin vitroand complete abolition of tumor growth and metastasisin vivo. Up-regulation of CaSm in NIH3T3 resulted in loss of contact inhibition and increased soft agar colony formationin vitro. The requirement for CaSm overexpression for neoplastic transformation confirms the concept that CaSm is a critical oncogene and potential target for molecular intervention. Furthermore, establishment of the murine clinically relevant model of pancreatic metastases provides a framework for the generation of preclinical data to support the development of novel molecular therapies targeting CaSm.