期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 4, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20200712
关键词
-
资金
- National Institutes of Health [CA175112, CA118113, CA178730, CA217482]
- Georgia Cancer Coalition
- Molecular Basis of Disease fellowship, Georgia State University
ProAgio, a protein targeting integrin α(v)β(3), induces apoptosis in CAFs and aECs, reduces intratumoral collagen and growth factor release, improves drug delivery, and decreases TNBC progression and metastasis.
Fibrotic tumor stroma plays an important role in facilitating triple-negative breast cancer (TNBC) progression and chemotherapeutic resistance. We previously reported a rationally designed protein (ProAgio) that targets integrin alpha(v)beta(3) at a novel site. ProAgio induces apoptosis via the integrin. Cancer-associated fibroblasts (CAFs) and angiogenic endothelial cells (aECs) in TNBC tumor express high levels of integrin alpha(v)beta(3). ProAgio effectively induces apoptosis in CAFs and aECs. The depletion of CAFs by ProAgio reduces intratumoral collagen and decreases growth factors released from CAFs in the tumor, resulting in decreased cancer cell proliferation and apoptotic resistance. ProAgio also eliminates leaky tumor angiogenic vessels, which consequently reduces tumor hypoxia and improves drug delivery. The depletion of CAFs and reduction in hypoxia by ProAgio decreases lysyl oxidase (LOX) secretion, which may play a role in the reduction of metastasis. ProAgio stand-alone or in combination with a chemotherapeutic agent provides survival benefit in TNBC murine models, highlighting the therapeutic potential of ProAgio as a treatment strategy.
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