Aligned forces: Origins and mechanisms of cancer dissemination guided by extracellular matrix architecture

Colorectal cancer dissemination depends on extracellular matrix genes related to remodeling and degradation of the matrix structure. This investigation intended to evaluate the association between FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 gene and protein expression levels in tumor tissue with clinical and histopathological neoplastic parameters of cancer dissemination. The expression associations between ECM molecules and selected epithelial markers EGFR, VEGF, Bcl2, P53, and KI-67 have also been examined in 114 patients with colorectal cancer who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry tissue microarray methods were performed in samples from the primary tumors. The gene expression results showed that the ITGA-3 and ITGB-5 genes were overexpressed in tumors with lymph node and distant metastasis (III/IV-stage tumors compared with I/II tumors). The MMP-2 gene showed significant overexpression in mucinous type tumors, and MMP-9 was overexpressed in villous adenocarcinoma histologic type tumors. The ECM genes MMP9 and ITGA-3 have shown a significant expression correlation with EGFR epithelial marker. The overexpression of the matrix extracellular genes ITGA-3 and ITGB-5 is associated with advanced stage tumors, and the genes MMP-2 and MMP-9 are overexpressed in mucinous and villous adenocarcinoma type tumors, respectively. The epithelial marker EGFR overactivity has been shown to be associated with the ECM genes MMP-9 and ITGA-3 expression.

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Structure and Function of a Prostate Cancer Dissemination–Permissive Extracellular Matrix

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-16-1516 ◽

2016 ◽

Vol 23 (9) ◽

pp. 2245-2254 ◽

Cited By ~ 25

Author(s):

Marie-France Penet ◽

Samata Kakkad ◽

Arvind P. Pathak ◽

Balaji Krishnamachary ◽

Yelena Mironchik ◽

...

Keyword(s):

Prostate Cancer ◽

Extracellular Matrix ◽

Structure And Function ◽

Cancer Dissemination ◽

And Function

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Inflammation-Generated Extracellular Matrix Fragments Drive Lung Metastasis

Cancer Growth and Metastasis ◽

10.1177/1179064417745539 ◽

2017 ◽

Vol 10 ◽

pp. 117906441774553 ◽

Cited By ~ 5

Author(s):

Sandrine Bekaert ◽

Marianne Fillet ◽

Benoit Detry ◽

Muriel Pichavant ◽

Raphael Marée ◽

...

Keyword(s):

Gene Expression ◽

Extracellular Matrix ◽

Tumor Cells ◽

Lung Parenchyma ◽

Chemotactic Activity ◽

Neutrophilic Inflammation ◽

Cancer Dissemination ◽

Metalloproteinase 9

Mechanisms explaining the propensity of a primary tumor to metastasize to a specific site still need to be unveiled, and clinical studies support a link between chronic inflammation and cancer dissemination to specific tissues. Using different mouse models, we demonstrate the role of inflammation-generated extracellular matrix fragments ac-PGP ( N-acetyl-proline-glycine-proline) on tumor cells dissemination to lung parenchyma. In mice exposed to cigarette smoke or lipopolysaccharide, lung neutrophilic inflammation produces increased levels of MMP-9 (matrix metalloproteinase 9) that contributes to collagen breakdown and allows the release of ac-PGP tripeptides. By silencing CXCR2 gene expression in tumor cells, we show that these generated ac-PGP tripeptides exert a chemotactic activity on tumor cells in vivo by binding CXCR2.

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Relationship between the Expression of the Extracellular Matrix Genes SPARC, SPP1, FN1, ITGA5 and ITGAV and Clinicopathological Parameters of Tumor Progression and Colorectal Cancer Dissemination

Oncology ◽

10.1159/000343436 ◽

2013 ◽

Vol 84 (2) ◽

pp. 81-91 ◽

Cited By ~ 38

Author(s):

Luciano de Souza Viana ◽

Renato José Affonso ◽

Sandra Regina Morini Silva ◽

Marcos Vinicius Araujo Denadai ◽

Delcio Matos ◽

...

Keyword(s):

Colorectal Cancer ◽

Extracellular Matrix ◽

Tumor Progression ◽

Clinicopathological Parameters ◽

Cancer Dissemination

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Cardiac myocytes cultured on a basement membrane extract of the ehs tumor

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142979 ◽

1986 ◽

Vol 44 ◽

pp. 270-271

Author(s):

L. Terracio ◽

A. Dewey ◽

K. Rubin ◽

T.K. Borg

Keyword(s):

Extracellular Matrix ◽

Basement Membrane ◽

Cardiac Myocytes ◽

Normal Tissue ◽

Cell Spreading ◽

Collagen Iv ◽

Basement Membrane Extract ◽

Membrane Extract ◽

Growth Development ◽

Multicellular Organisms

The recognition and interaction of cells with the extracellular matrix (ECM) effects the normal physiology as well as the pathology of all multicellular organisms. These interactions have been shown to influence the growth, development, and maintenance of normal tissue function. In previous studies, we have shown that neonatal cardiac myocytes specifically interacts with a variety of ECM components including fibronectin, laminin, and collagens I, III and IV. Culturing neonatal myocytes on laminin and collagen IV induces an increased rate of both cell spreading and sarcomerogenesis.

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Neutrophil migration through in vitro interstitial matrix

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100124872 ◽

1992 ◽

Vol 50 (1) ◽

pp. 894-895

Author(s):

J. Roemer ◽

S.R. Simon

Keyword(s):

Extracellular Matrix ◽

Smooth Muscle ◽

Cell Migration ◽

Smooth Muscle Cells ◽

Inflammatory Cell ◽

Neutrophil Migration ◽

Culture Conditions ◽

Aortic Smooth Muscle ◽

Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

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The extracellular matrix of echinoderm and amphibian eggs: Visualization in quick-frozen, deep-etched, and rotary-shadowed specimens

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010015784x ◽

1990 ◽

Vol 48 (3) ◽

pp. 60-61

Author(s):

Barry Bonnell ◽

Carolyn Larabell ◽

Douglas Chandler

Keyword(s):

Extracellular Matrix ◽

Plasma Membrane ◽

Sea Urchin ◽

Crystalline Structure ◽

Cortical Granule ◽

Two Dimensional ◽

Small Peptides ◽

Deep Etching ◽

Quick Freezing ◽

Acrosomal Reaction

Eggs of many species including those of echinoderms, amphibians and mammals exhibit an extensive extracellular matrix (ECM) that is important both in the reception of sperm and in providing a block to polyspermy after fertilization.In sea urchin eggs there are two distinctive coats, the vitelline layer which contains glycoprotein sperm receptors and the jelly layer that contains fucose sulfate glycoconjugates which trigger the acrosomal reaction and small peptides which act as chemoattractants for sperm. The vitelline layer (VL), as visualized by quick-freezing, deep-etching, and rotary-shadowing (QFDE-RS), is a fishnet-like structure, anchored to the plasma membrane by short posts. Orbiting above the VL are horizontal filaments which are thought to anchor the thicker jelly layer to the egg. Upon fertilization, the VL elevates and is transformed by cortical granule secretions into the fertilization envelope (FE). The rounded casts of microvilli in the VL are transformed into angular peaks and the envelope becomes coated inside and out with sheets of paracrystalline protein having a quasi-two dimensional crystalline structure.

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Extracellular matrix: the gatekeeper of tumor angiogenesis

Biochemical Society Transactions ◽

10.1042/bst20190653 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1543-1555 ◽

Cited By ~ 10

Author(s):

Maurizio Mongiat ◽

Simone Buraschi ◽

Eva Andreuzzi ◽

Thomas Neill ◽

Renato V. Iozzo

Keyword(s):

Extracellular Matrix ◽

Tumor Angiogenesis ◽

Signaling Cascades ◽

Cancer Growth ◽

Cell Behavior ◽

Metastatic Progression ◽

Surface Receptors ◽

The Matrix ◽

Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

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