Three-dimensional context regulation of metastasis
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TLDR
Synergistic interactions between matrix remodeling and tumor hypoxia influence common mechanisms that maximize tumor progression and cooperate to drive metastasis, which should identify novel therapeutic targets.Abstract:
Tumor progression ensues within a three-dimensional microenvironment that consists of cellular and non-cellular components. The extracellular matrix (ECM) and hypoxia are two non-cellular components that potently influence metastasis. ECM remodeling and collagen cross-linking stiffen the tissue stroma to promote transformation, tumor growth, motility and invasion, enhance cancer cell survival, enable metastatic dissemination, and facilitate the establishment of tumor cells at distant sites. Matrix degradation can additionally promote malignant progression and metastasis. Tumor hypoxia is functionally linked to altered stromal-epithelial interactions. Hypoxia additionally induces the expression of pro-migratory, survival and invasion genes, and up-regulates expression of ECM components and modifying enzymes, to enhance tumor progression and metastasis. Synergistic interactions between matrix remodeling and tumor hypoxia influence common mechanisms that maximize tumor progression and cooperate to drive metastasis. Thus, clarifying the molecular pathways by which ECM remodeling and tumor hypoxia intersect to promote tumor progression should identify novel therapeutic targets.read more
Citations
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Journal ArticleDOI
Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
Kandice R. Levental,Hongmei Yu,Laura Kass,Johnathon N. Lakins,Mikala Egeblad,Janine T. Erler,Sheri F. T. Fong,Katalin Csiszar,Amato J. Giaccia,Wolfgang Weninger,Mitsuo Yamauchi,David L. Gasser,Valerie M. Weaver +12 more
TL;DR: Reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence, and data show how collagenCrosslinking can modulate tissue fibrosis and stiffness to force focal adhesion, growth factor signaling and breast malignancies.
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The extracellular matrix at a glance
TL;DR: The extracellular matrix is the non-cellular component present within all tissues and organs, and provides not only essential physical scaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue development.
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Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer
Thomas R. Cox,Janine T. Erler +1 more
TL;DR: Current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression are discussed, and how improving understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies.
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Tumors as Organs: Complex Tissues that Interface with the Entire Organism
TL;DR: Understanding the complex ways in which cancer cells interact with their surroundings, both locally in the tumor organ and systemically in the body as a whole, has implications for effective cancer prevention and therapy.
Journal ArticleDOI
The Matrisome: In Silico Definition and In Vivo Characterization by Proteomics of Normal and Tumor Extracellular Matrices
Alexandra Naba,Karl R. Clauser,Sebastian Hoersch,Sebastian Hoersch,Hui Liu,Steven A. Carr,Richard O. Hynes +6 more
TL;DR: A proteomic strategy developed to characterize the in vivo ECM composition of normal tissues and tumors using enrichment of protein extracts for ECM components and subsequent analysis by mass spectrometry and a bioinformatic approach to predict the in silico “matrisome” defined as the ensemble of ECM proteins and associated factors are presented.
References
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