The Experts below are selected from a list of 50283 Experts worldwide ranked by ideXlab platform
Ivan Stamenkovic - One of the best experts on this subject based on the ideXlab platform.
-
matrix metalloproteinases in Tumor Invasion and metastasis
Seminars in Cancer Biology, 2000Co-Authors: Ivan StamenkovicAbstract:Abstract Extensive work on the mechanisms of Tumor Invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie Tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as Tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance Tumor survival, Invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote Tumor development has been thought to be the proteolytic breakdown of tissue barriers to Invasion and the associated facilitation of circulating Tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following Invasion of blood vessels) and regulate the relationship between Tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include latent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence Tumor behavior.
-
cell surface localized matrix metalloproteinase 9 proteolytically activates tgf β and promotes Tumor Invasion and angiogenesis
Genes & Development, 2000Co-Authors: Qin Yu, Ivan StamenkovicAbstract:We have uncovered a novel functional relationship between the hyaluronan receptor CD44, the matrix metalloproteinase-9 (MMP-9) and the multifunctional cytokine TGF-β in the control of Tumor-associated tissue remodeling. CD44 provides a cell surface docking receptor for proteolytically active MMP-9 and we show here that localization of MMP-9 to cell surface is required for its ability to promote Tumor Invasion and angiogenesis. Our observations also indicate that MMP-9, as well as MMP-2, proteolytically cleaves latent TGF-β, providing a novel and potentially important mechanism for TGF-β activation. In addition, we show that MMP-9 localization to the surface of normal keratinocytes is CD44 dependent and can activate latent TGF-β. These observations suggest that coordinated CD44, MMP-9, and TGF-β function may provide a physiological mechanism of tissue remodeling that can be adopted by malignant cells to promote Tumor growth and Invasion.
-
localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for cd44 mediated Tumor Invasion
Genes & Development, 1999Co-Authors: Qin Yu, Ivan StamenkovicAbstract:The cell surface hyaluronan receptor CD44 promotes Tumor growth and metastasis by mechanisms that remain poorly understood. We show here that CD44 associates with a proteolytic form of the matrix metalloproteinase-9 (MMP-9) on the surface of mouse mammary carcinoma and human melanoma cells. CD44-associated cell surface MMP-9 promotes cell-mediated collagen IV degradation in vitro and mediates Tumor cell Invasion of G8 myoblast monolayers. Several distinct CD44 isoforms coprecipitate with MMP-9 and CD44/MMP-9 coclustering is observed to be dependent on the ability of CD44 to form hyaluronan-induced aggregates. Disruption of CD44/MMP-9 cluster formation, by overexpression of soluble or truncated cell surface CD44, is shown to inhibit Tumor invasiveness in vivo. Our observations indicate that CD44 serves to anchor MMP-9 on the cell surface and define a mechanism for CD44-mediated Tumor Invasion.
Timothy Errington - One of the best experts on this subject based on the ideXlab platform.
-
Registered report: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors Tumor Invasion and metastasis
eLife, 2015Co-Authors: Steven N. Fiering, Judith Lacoste, Lay Hong Ang, Tim D. Smith, Erin Griner, Fraser Tan, Joelle Lomax, William Gunn, Elizabeth Iorns, Timothy ErringtonAbstract:Mechanotransduction is a key determinant of tissue homeostasis and Tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intraTumoral microenvironments to facilitate Tumor Invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment. PaperFlick: © 2011 Elsevier Inc.
Robert J Gillies - One of the best experts on this subject based on the ideXlab platform.
-
acid mediated Tumor Invasion a multidisciplinary study
Cancer Research, 2006Co-Authors: Robert A Gatenby, Edward T Gawlinski, Arthur F Gmitro, Brant M Kaylor, Robert J GilliesAbstract:The acid-mediated Tumor Invasion hypothesis proposes altered glucose metabolism and increased glucose uptake, observed in the vast majority of clinical cancers by fluorodeoxyglucose-positron emission tomography, are critical for development of the invasive phenotype. In this model, increased acid production due to altered glucose metabolism serves as a key intermediate by producing H + flow along concentration gradients into adjacent normal tissue. This chronic exposure of periTumoral normal tissue to an acidic microenvironment produces toxicity by: ( a ) normal cell death caused by the collapse of the transmembrane H + gradient inducing necrosis or apoptosis and ( b ) extracellular matrix degradation through the release of cathepsin B and other proteolytic enzymes. Tumor cells evolve resistance to acid-induced toxicity during carcinogenesis, allowing them to survive and proliferate in low pH microenvironments. This permits them to invade the damaged adjacent normal tissue despite the acid gradients. Here, we describe theoretical and empirical evidence for acid-mediated Invasion. In silico simulations using mathematical models provide testable predictions concerning the morphology and cellular and extracellular dynamics at the Tumor-host interface. In vivo experiments confirm the presence of periTumoral acid gradients as well as cellular toxicity and extracellular matrix degradation in the normal tissue exposed to the acidic microenvironment. The acid-mediated Tumor Invasion model provides a simple mechanism linking altered glucose metabolism with the ability of Tumor cells to form invasive cancers. (Cancer Res 2006; 66(10): 5216-23)
Minsik Kim - One of the best experts on this subject based on the ideXlab platform.
-
diagnostic accuracy of magnetic resonance imaging mri in the assessment of Tumor Invasion depth in oral oropharyngeal cancer
Oral Oncology, 2011Co-Authors: Junook Park, So Lyung Jung, Yonghoon Joo, Chan Kwon Jung, Kwangjae Cho, Minsik KimAbstract:The purpose of the present study was to evaluate the diagnostic value of MRI for measuring Invasion depth in oral/oropharyngeal carcinoma. We retrospectively reviewed pathologic specimens and MRI findings of 114 patients who were diagnosed with squamous cell carcinoma of the oral cavity and oropharynx. Invasion depths were evaluated in pathologic specimens and by MRI. The mean histologic and MRI Invasion depths were 13.57 ± 8.476 and 15.24 ± 10.700 mm, respectively. The overall Pearson’s correlation coefficient for histologic and MRI (T1W-MRI) Invasion depths was 0.825, which was statistically significant (P < 0.001). Pearson’s correlation coefficients for histologic and MRI Invasion depths in oral tongue, tongue base, and tonsil cancers were 0.949, 0.941, and 0.578, respectively. The MRI Invasion depth was significantly different according to nodal status in cancers of the oral tongue (P = 0.001∗) and tongue base (P = 0.003∗). With MRI, the Invasion depth cutoff values for determining positive nodes were 9.5 and 14.5 mm in cancers of the oral tongue and tongue base, respectively. Preoperative MRI is an accurate method for measuring Tumor Invasion depth in oral tongue and tongue base cancers. Furthermore, it has predictive value for nodal metastasis in the oral tongue and tongue base.
Steven N. Fiering - One of the best experts on this subject based on the ideXlab platform.
-
Registered report: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors Tumor Invasion and metastasis
eLife, 2015Co-Authors: Steven N. Fiering, Judith Lacoste, Lay Hong Ang, Tim D. Smith, Erin Griner, Fraser Tan, Joelle Lomax, William Gunn, Elizabeth Iorns, Timothy ErringtonAbstract:Mechanotransduction is a key determinant of tissue homeostasis and Tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intraTumoral microenvironments to facilitate Tumor Invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment. PaperFlick: © 2011 Elsevier Inc.
