期刊
CANCER DISCOVERY
卷 2, 期 12, 页码 1150-1165出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-12-0216
关键词
-
类别
资金
- Dana-Farber/Harvard Breast Cancer SPORE NCI [2 P50 CA89393-06]
- Dana Farber/Harvard Cancer Center Kidney Cancer SPORE [P50 CA101942]
- NIH NHLBI [K08HL097070]
- Malcolm Hecht Jr. Hematology Research Endowment
- Dana Farber/Harvard Cancer Center Breast Cancer SPORE NCI [5 P30 CA006516-46-2010-01-NN-02]
- Harvard Stem Cell Institute
- BWH Biomedical Research Institute
Breast cancer recurrence rates vary following treatment, suggesting that tumor cells disseminate early from primary sites but remain indolent indefinitely before progressing to symptomatic disease. The reasons why some indolent disseminated tumors erupt into overt disease are unknown. We discovered a novel process by which certain luminal breast cancer (LBC) cells and patient tumor specimens (LBC instigators) establish a systemic macroenvironment that supports outgrowth of otherwise-indolent disseminated tumors (responders). Instigating LBCs secrete cytokines that are absorbed by platelets, which are recruited to responding tumor sites where they aid vessel formation. Instigator-activated bone marrow cells enrich responding tumor cell expression of CD24, an adhesion molecule for platelets, and provide a source of VEGF receptor 2(+) tumor vessel cells. This cascade results in growth of responder adenocarcinomas and is abolished when platelet activation is inhibited by aspirin. These findings highlight the macroenvironment as an important component of disease progression that can be exploited therapeutically. SIGNIFICANCE: Currently, processes that mediate progression of otherwise indolent tumors are not well understood, making it difficult to accurately predict which cancer patients are likely to relapse. Our findings highlight the macroenvironment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from adjuvant therapy. Cancer Discov; 2(12); 1150-65. (C) 2012 AACR.
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