Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth.
Kazuyoshi Shiga,Masayasu Hara,Takaya Nagasaki,Takafumi Sato,Hiroki Takahashi,Hiromitsu Takeyama +5 more
TLDR
It is shown that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions, and CAFs contribute to drug-resistance acquisition in cancer cells.Abstract:
Cancer tissues are composed of cancer cells and the surrounding stromal cells (e.g., fibroblasts, vascular endothelial cells, and immune cells), in addition to the extracellular matrix. Most studies investigating carcinogenesis and the progression, invasion, metastasis, and angiogenesis of cancer have focused on alterations in cancer cells, including genetic and epigenetic changes. Recently, interactions between cancer cells and the stroma have attracted considerable attention, and increasing evidence has accumulated on this. Several researchers have gradually clarified the origins, features, and roles of cancer-associated fibroblasts (CAFs), a major component of the cancer stroma. CAFs function in a similar manner to myofibroblasts during wound healing. We previously reported the relationship between CAFs and angiogenesis. Interleukin-6 (IL-6), a multifunctional cytokine, plays a central role in regulating inflammatory and immune responses, and important roles in the progression, including proliferation, migration, and angiogenesis, of several cancers. We showed that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions. Furthermore, CAFs contribute to drug-resistance acquisition in cancer cells. The interaction between cancer cells and the stroma could be a potential target for anti-cancer therapy.read more
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DissertationDOI
Integrating In-Silico Models with In-Vitro Data to Generate Novel Insights into Biological Systems
TL;DR: These models exhibit how integration of in-silico models with in-vitro datasets can be used to generate new knowledge, or testable hypotheses, in reliable, well parameterised systems capable of replicating dynamical properties of the biological systems.
Journal ArticleDOI
Embryonic protein NODAL regulates the breast tumor microenvironment by reprogramming cancer-derived secretomes
Dylan Dieters-Castator,Paola M. Dantonio,Matt Piaseczny,Guihua Zhang,Jiahui Liu,Miljan Kuljanin,Stephen E. Sherman,Michael Jewer,Katherine Quesnel,Eun Young Kang,Martin Köbel,Gabrielle M. Siegers,Andrew Leask,David A. Hess,Gilles A. Lajoie,Lynne-Marie Postovit,Lynne-Marie Postovit +16 more
TL;DR: In this paper, the secreted embryonic protein NODAL was shown to correlate with the presence of activated fibroblasts in human triple-negative breast cancers and that it directly induces Cancer-associated fibroblast phenotypes.
Patent
Ltbp complex-specific inhibitors of tgf-beta and uses thereof
Thomas Schurpf,Justin W. Jackson,George Coricor,Abhishek Datta,Stefan Wawersik,Christopher Littlefield,Adam Fogel +6 more
TL;DR: In this paper, the authors present inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGFβ and/or LTBP3-tGFβ.
Journal ArticleDOI
Geostatistical Modeling and Heterogeneity Analysis of Tumor Molecular Landscape
TL;DR: A new computational platform, GATHER, for geostatistical modeling of single cell RNA-seq data to synthesize high-resolution and continuous gene expression landscapes of a given tumor sample to study hallmarks of cancer in the phenotypic contexts defined by cancer associated fibroblasts.
References
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