纤维瘤病
侵袭性纤维瘤病
生物
癌症研究
肿瘤进展
运动性
免疫组织化学
细胞生长
突变
透明质酸
病理
免疫学
癌症
基因
细胞生物学
医学
遗传学
作者
Cornelia Tölg,Raymoond Poon,Riccardo Fodde,Eva A. Turley,Benjamin A. Alman
出处
期刊:Oncogene
[Springer Nature]
日期:2003-10-09
卷期号:22 (44): 6873-6882
被引量:93
标识
DOI:10.1038/sj.onc.1206811
摘要
Aggressive fibromatosis (desmoid tumor) is a locally invasive soft tissue neoplasm associated with mutations resulting in beta-catenin-mediated transcriptional activation. This tumor is composed of cells with histological and molecular characteristics common to proliferating mesenchymal cells of dermal wounds. Using immunohistochemistry and RT-PCR, we show that Rhamm, a protein with an important role in wound healing and neoplastic progression, is also expressed at high levels in aggressive fibromatosis. A mouse harboring a targeted deletion in Rhamm was generated, resulting in viable Rhamm-/- animals. Rhamm-/- mice were crossed with Apc/Apc1638N mice, which harbor a targeted mutation in the Apc gene predisposing animals to gastrointestinal and aggressive fibromatosis tumors. Rhamm deficiency significantly decreased the number of aggressive fibromatosis tumors formed, but did not alter the number of gastrointestinal polyps. Cell culture studies show that Rhamm regulates cell proliferation in both fibroblasts and fibromatosis cells under conditions of low density, but not high density. These results suggest that Rhamm regulates proliferation of cells with sparse cell-cell contacts, such as occurs in aggressive fibromatosis; provides the first genetic evidence implicating Rhamm in tumor pathology; and suggest Rhamm blockade as a potential therapeutic target for this otherwise difficult-to-treat neoplasm.
科研通智能强力驱动
Strongly Powered by AbleSci AI