Characterization of Extracellular Matrix-induced Molecular Mechanisms of Cancer Cell Resistance in 2- and 3-dimensional Culture Systems

Characterization of Extracellular Matrix-induced Molecular Mechanisms of Cancer Cell Resistance in 2- and 3-dimensional Culture Systems PDF Author: Nilly Shimony
Publisher:
ISBN:
Category :
Languages : en
Pages : 210

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Chapter: 'Analysis of Breast Cancer Cell Invasion Using an Organotypic Culture System' from Book: 3D Cell Culture: Methods and Protocols

Chapter: 'Analysis of Breast Cancer Cell Invasion Using an Organotypic Culture System' from Book: 3D Cell Culture: Methods and Protocols PDF Author: Romana E. Ranftl
Publisher:
ISBN:
Category :
Languages : en
Pages : 13

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Metastasis is the main cause of cancer patient mortality. Local tumor invasion is a key step in metastatic dissemination whereby cancer cells dislodge from primary tumors, migrate through the peritumoral stroma and reach the circulation. This is a highly dynamic process occurring in three dimensions that involves interactions between tumor, stromal cells, and the extracellular matrix. Here we describe the organotypic culture system and its utility to study breast cancer cell invasion induced by cancer-associated fibroblasts. This is a three-dimensional model that reproduces the biochemical and physiological properties of real tissue and allows for investigating the molecular and cellular mechanisms involving tumor and its microenvironment, and their contribution to cancer cell invasion. This system provides a robust, accurate, and reproducible method for measuring cancer cell invasion and represents a valuable tool to improve the mechanistic understanding of the initial steps in metastasis.

Comparative Oncology

Comparative Oncology PDF Author: Alecsandru Ioan Baba
Publisher:
ISBN: 9789732714577
Category : Electronic books
Languages : en
Pages : 787

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Fibroblast-derived Extracellular Matrix

Fibroblast-derived Extracellular Matrix PDF Author: Michael Thomas Scherzer
Publisher:
ISBN:
Category : Extracellular matrix
Languages : en
Pages : 66

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Poor lung cancer survival can largely be contributed to the metastatic cells that invade and spread throughout the body. The tumor microenvironment (TME) is composed of multiple cell types, as well as non-cellular components. The TME plays a critical role in the development of metastatic cancers by providing migratory cues that change the growing tumor's properties. The Extracellular Matrix (ECM), a main component of the TME, has been shown to change composition during tumor progression, allowing cancer cells to invade tissue and survive away from the primary cancer site. Although the ECM is well-known to influence the fate of tumor progression, little is known about the molecular mechanisms that are affected by the cancer cell-ECM interactions. It is imperative that these mechanisms are understood in order to properly understand and prevent lung cancer dissemination. However, common in vitro studies do not incorporate these interactions into everyday cell culture assays. In our lab, we have adopted a model that examines decellularized human fibroblast-derived ECM as a 3D substrate for growth of lung adenocarcinoma cell lines. It is hypothesized that the interactions between lung cancer cell lines and fibroblast-derived ECM will alter phenotypes important for lung cancer progression. Here, we have characterized the effect of various fibroblast-derived matrices on the properties of various lung cancer adenocarcinoma cell lines. Such altered processes include morphology, growth, and migration. This work highlights the significance of the cell-ECM interaction and its requirement for incorporation into in vitro experiments. Implementation of a fibroblast-derived ECM as an in vitro technique will provide researchers with an important factor to manipulate to better recreate and study the TME.

Extracellular Matrix Degradation

Extracellular Matrix Degradation PDF Author: William C. Parks
Publisher: Springer Science & Business Media
ISBN: 3642168612
Category : Science
Languages : en
Pages : 262

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Book Description
Regulated turnover of extracellular matrix (ECM) is an important component of tissue homeostasis. In recent years, the enzymes that participate in, and control ECM turnover have been the focus of research that touches on development, tissue remodeling, inflammation and disease. This volume in the Biology of Extracellular Matrix series provides a review of the known classes of proteases that degrade ECM both outside and inside the cell. The specific EMC proteases that are discussed include cathepsins, bacterial collagenases, matrix metalloproteinases, meprins, serine proteases, and elastases. The volume also discusses the domains responsible for specific biochemical characteristics of the proteases and the physical interactions that occur when the protease interacts with substrate. The topics covered in this volume provide an important context for understanding the role that matrix-degrading proteases play in normal tissue remodeling and in diseases such as cancer and lung disease.

Tumor Organoids

Tumor Organoids PDF Author: Shay Soker
Publisher: Humana Press
ISBN: 3319605119
Category : Medical
Languages : en
Pages : 225

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Book Description
Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.

Extracellular Matrix Mechanics Regulate Cell Signaling and Migratory Potential in Cancer

Extracellular Matrix Mechanics Regulate Cell Signaling and Migratory Potential in Cancer PDF Author: Jaya Srivastava
Publisher:
ISBN:
Category :
Languages : en
Pages : 326

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Book Description
The objective of the presented research is to examine the relationship between the cellular microenvironment and biochemical response of metastatic cells. Clinically recognized as a trait of cancer progression, the cellular microenvironment can have variable and distinct mechanical properties that are processed via cellular mechanosensing, resulting in a cellular biochemical response. A range of studies investigating the interactions between the cellular micromechanical environment and the cell's molecular response during disease progression have been made, yet remain absent of quantitative characterization of many of these coordinated responses. The fundamental inquiry that drives the following research attempts to elucidate how a cell perceives the physical microenvironment and converts that signal to a biochemical response. With the goal of providing insight to such responses, the presented research seeks to elucidate the following questions: (1) What are the integrated effects of ECM stiffness, ECM architecture, and breast cancer cell metastatic potential on cell migration? (2) How does endogenous tissue transglutaminase (tTG) cross-linking of the ECM scaffold effect ECM mechanical properties? (3) How does the architecture and stiffness of the extracellular matrix (ECM) effect the systems-level cellular migration and signaling response? (4) What are the integrated effects of ECM architecture and the targeted knockdown of integrin [beta]1 and MT1-MMP on cellular metastatic potential? The presented research utilizes an interdisciplinary approach, integrating experimental mechanics, biochemical analysis, cellular biology techniques, covalent chemistry, and various microscopy techniques, to investigate these events. In short, cancerous cells are cultured atop or within synthetic collagen type I ECMs of varying mechanical stiffness and structure. These cells are subsequently analyzed by molecular analysis and immunoassays, including quantitative PCR, Western blotting, and gelatin zymography, to acquire measures of the cellular response to perturbations of micromechanical environment. Time-lapse microscopy experiments and subsequent image analyses enable observations of cellular migratory potential through synthetic ECMs. Results indicate that cooperative synergy between ECM properties, cell-matrix adhesion, and pericellular proteolysis drive cell migratory potential of highly invasive tumorigenic cell populations. Collectively, these findings contribute to the cancer biology and mechanobiology fields by systematically extending current insights of matrix mechanics, cellular signaling, and cellular migratory potential in cancer.

Biomechanics in Oncology

Biomechanics in Oncology PDF Author: Cheng Dong
Publisher: Springer
ISBN: 3319952943
Category : Medical
Languages : en
Pages : 376

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Book Description
This book covers multi-scale biomechanics for oncology, ranging from cells and tissues to whole organ. Topics covered include, but not limited to, biomaterials in mechano-oncology, non-invasive imaging techniques, mechanical models of cell migration, cancer cell mechanics, and platelet-based drug delivery for cancer applications. This is an ideal book for graduate students, biomedical engineers, and researchers in the field of mechanobiology and oncology. This book also: Describes how mechanical properties of cancer cells, the extracellular matrix, tumor microenvironment and immuno-editing, and fluid flow dynamics contribute to tumor progression and the metastatic process Provides the latest research on non-invasive imaging, including traction force microscopy and brillouin confocal microscopy Includes insight into NCIs’ role in supporting biomechanics in oncology research Details how biomaterials in mechano-oncology can be used as a means to tune materials to study cancer

Extracellular Matrix Components

Extracellular Matrix Components PDF Author: Erkki Ruoslahti
Publisher: Academic Press
ISBN:
Category : Medical
Languages : en
Pages : 680

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Book Description
This publication presents a collection of essays that reflect current research and technical advances in extracellular matrix field, which has undergone remarkable expansion since publication of Volume 82 of 'Methods in Enzymology' in 1982.

Multi-Drug Resistance in Cancer

Multi-Drug Resistance in Cancer PDF Author: Jun Zhou
Publisher: Humana Press
ISBN: 9781617796647
Category : Medical
Languages : en
Pages : 492

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Book Description
Chemotherapy is one of the major treatment options for cancer patients; however, the efficacy of chemotherapeutic management of cancer is severely limited by multidrug resistance, in that cancer cells become simultaneously resistant to many structurally and mechanistically unrelated drugs. In the past three decades, a number of mechanisms by which cancer cells acquire multidrug resistance have been discovered. In addition, the development of agents or strategies to overcome resistance has been the subject of intense study. This book contains comprehensive and up-to-date reviews of multidrug resistance mechanisms, from over-expression of ATP-binding cassette drug transporters such as P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance p- tein to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The book also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression. In addition, this book contains techniques for the detection and imaging of drug transporters, methods for the investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. The book intends to provide a state-of-the-art collection of reviews and methods for both basic and clinician investigators who are interested in cancer multidrug resistance mechanisms and reversal strategies. Tianjin, China Jun Zhou v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Multidrug Resistance in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bruce C. Baguley 2 Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . .