期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 35, 页码 15559-15564出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1003034107
关键词
metastasis; tumorigenesis
资金
- Terry Fox Foundation through the National Cancer Institute of Canada
- Canada Research Chair in Molecular Oncology
- Cancer Research United Kingdom
- Canadian Institutes of Health Research/Canadian Breast Cancer Research Alliance
- Terry Fox Foundation
- US Department of Defense
- National Institutes of Health [5P01GA-099031-05]
Cross-talk between integrin receptors and activated growth factor receptors has been hypothesized to play a critical role in the initiation and progression of cancer. Despite in vitro evidence documenting the important role of integrin receptors in the regulation of cancer cell proliferation, the relative contribution of the integrin receptors to the initiation and progression of tumors remains unclear. Previous studies with a polyomavirus middle T mammary tumor model have indicated that targeted disruption of beta 1-integrin in the mammary glands of these mice completely blocks tumor induction. To further explore the general significance of these observations, we have crossed these conditional beta 1-integrin strains to a strain of mice carrying mouse mammary tumor virus/activated erbB2 (herein referred to as the NIC strain). In contrast to the tumor induction block in the polyomavirus middle T model, tumor onset in the beta 1-integrin-deficient NIC mice was delayed by only 30 d and was 100% penetrant. This modest effect on tumor induction was not a result of inefficient excision, as all tumors were confirmed as beta 1-integrin-null. Animals bearing beta 1-integrin-deficient ErbB2 tumors exhibited significantly reduced tumor volume, which was associated with increased tumor cell apoptosis and a reduction in tumor angiogenesis. In addition, beta 1-integrin-deficient tumors were compromised in their capacity to metastasize to the lung, a - deficiency associated with abrogation of adhesion signaling. Taken together, these observations suggest that, although beta 1-integrin is dispensable for the initiation of ErbB2 tumor induction, it plays a critical role in metastatic phase of tumor progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据