期刊
FRONTIERS IN IMMUNOLOGY
卷 14, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2023.1154528
关键词
extracellular matrix; fibroblasts; mechanics; models; desmoplasia; pancreatic cancer; breast cancer
类别
The desmoplastic reaction observed in many cancers, particularly in breast and pancreatic cancer, is a significant indicator of disease progression and prognosis. Alterations in stromal-derived extracellular matrix (ECM) within desmoplasia play a crucial role in driving cancer progression. Using fibroblast-derived matrices (FDMs), it was found that cancer cells have increased growth on cancer associated FDMs compared to FDMs derived from non-malignant tissue fibroblasts. Compositional, structural, and mechanical analyses revealed significant differences in ECM characteristics between normal and cancer-associated stroma at the primary tumor site.
The desmoplastic reaction observed in many cancers is a hallmark of disease progression and prognosis, particularly in breast and pancreatic cancer. Stromal-derived extracellular matrix (ECM) is significantly altered in desmoplasia, and as such plays a critical role in driving cancer progression. Using fibroblast-derived matrices (FDMs), we show that cancer cells have increased growth on cancer associated FDMs, when compared to FDMs derived from non-malignant tissue (normal) fibroblasts. We assess the changes in ECM characteristics from normal to cancer-associated stroma at the primary tumor site. Compositional, structural, and mechanical analyses reveal significant differences, with an increase in abundance of core ECM proteins, coupled with an increase in stiffness and density in cancer-associated FDMs. From compositional changes of FDM, we derived a 36-ECM protein signature, which we show matches in large part with the changes in pancreatic ductal adenocarcinoma (PDAC) tumor and metastases progression. Additionally, this signature also matches at the transcriptomic level in multiple cancer types in patients, prognostic of their survival. Together, our results show relevance of FDMs for cancer modelling and identification of desmoplastic ECM components for further mechanistic studies.
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