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
Citations
More filters
Journal ArticleDOI
Targeting the tumour stroma to improve cancer therapy
TL;DR: An overview of the advances in understanding the complex cancer cell–tumour stroma interactions is provided and how this knowledge can result in more effective therapeutic strategies, which might ultimately improve patient outcomes are discussed.
Journal ArticleDOI
Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment
TL;DR: This review article summarized the recent progress in various nanoformulations for cancer therapy, with a special emphasis on tumour microenvironment stimuli-responsive ones, which it believes offer a good chance for the practical translation of nanoparticle formulas into clinic.
Journal ArticleDOI
Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer
TL;DR: The key roles of the IL-6 cytokine family in regulating innate and adaptive immunity, as well as other physiological responses are considered, which highlight the potential of targeting IL- 6 family members to treat inflammatory diseases and cancer.
Book ChapterDOI
Tumor-Derived Exosomes and Their Role in Cancer Progression.
TL;DR: Tumor-derived exosomes may interfere with cancer immunotherapy, but they also could serve as adjuvants and antigenic components of antitumor vaccines and are of potential interest as noninvasive biomarkers of cancer.
Journal ArticleDOI
Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas
Reuben Moncada,Dalia Barkley,Florian Wagner,Marta Chiodin,Joseph C. Devlin,Maayan Baron,Cristina H. Hajdu,Diane M. Simeone,Itai Yanai +8 more
TL;DR: Applying multimodal intersection analysis to primary pancreatic tumors, it is found that subpopulations of ductal cells, macrophages, dendritic cells and cancer cells have spatially restricted enrichments, as well as distinct coenrichments with other cell types.
References
More filters
Journal ArticleDOI
Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis
TL;DR: The VEGF/VPF ligands and receptors are crucial regulators of vasculogenesis, angiogenesis, lymphangiogenesis and vascular permeability in vertebrates and mapping the signaling system of these important receptors may provide the knowledge necessary to suppress specific signaling pathways in major human diseases.
Journal ArticleDOI
Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein–α
Matthew Kraman,Paul J. Bambrough,James N. Arnold,Edward W. Roberts,Lukasz Magiera,James O. Jones,Aarthi Gopinathan,David A. Tuveson,Douglas T. Fearon +8 more
TL;DR: Findings reveal that multiple cell types contribute to the immunosuppressive tumor microenvironment and will inform therapeutic cancer vaccine design.
Journal ArticleDOI
Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth.
Michael Quante,Shui Ping Tu,Shui Ping Tu,Hiroyuki Tomita,Tamas A. Gonda,Sophie S.W. Wang,Shigeo Takashi,Gwang Ho Baik,Wataru Shibata,Bethany DiPrete,Kelly S. Betz,Richard A. Friedman,Andrea Varro,Benjamin Tycko,Timothy C. Wang +14 more
TL;DR: It is shown that at least 20% of CAFs originate from bone marrow (BM) and derive from mesenchymal stem cells (MSCs), and αSMA+ myofibroblasts (MFs) are niche cells normally present in BM and increase markedly during cancer progression.
Journal ArticleDOI
Discovery of Endothelial to Mesenchymal Transition as a Source for Carcinoma-Associated Fibroblasts
TL;DR: It is shown that transforming growth factor-beta1 could induce proliferating endothelial cells to undergo a phenotypic conversion into fibroblast-like cells and EndMT is a unique mechanism for the accumulation of carcinoma-associated fibroblasts and suggested that antiangiogenic treatment of tumors may have a direct effect in decreasing activated fibro Blasts that likely facilitate cancer progression.
Journal ArticleDOI
The Fibronectin Domain ED-A Is Crucial for Myofibroblastic Phenotype Induction by Transforming Growth Factor-β1
Guido Serini,Marie-Luce Bochaton-Piallat,Patricia Ropraz,Antoine Geinoz,Laura Borsi,Luciano Zardi,Giulio Gabbiani +6 more
TL;DR: It is reported here that ED-A FN deposition precedes α-SM actin expression by fibroblasts during granulation tissue evolution in vivo and after TGFβ1 stimulation in vitro, and a hitherto unknown mechanism of cytokine-determined gene stimulation based on the generation of an ECM-derived permissive outside in signaling is identified.