An Investigation Into the Means and Methods Through which Breast Cancer Cells are Able to Migrate PDF Download
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Author: Rachel Avard
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
We repeatedly demonstrate the importance of in vitro, 3D cell culture in the study of breast cancer migration. Using such cell culture techniques, we outline previously unknown aspects of breast cancer cellular migration both in regards to the importance of blebs and to the gain of function activity of mutant p53, the latter of which was made possible through use of the DISC-3D protocol. We argue that continued study in this area will provide insights into how breast cancer cells migrate, providing paths and new treatment strategies for preventing such migration.
Author: Rachel Avard
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
We repeatedly demonstrate the importance of in vitro, 3D cell culture in the study of breast cancer migration. Using such cell culture techniques, we outline previously unknown aspects of breast cancer cellular migration both in regards to the importance of blebs and to the gain of function activity of mutant p53, the latter of which was made possible through use of the DISC-3D protocol. We argue that continued study in this area will provide insights into how breast cancer cells migrate, providing paths and new treatment strategies for preventing such migration.
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309183952
Category : Medical
Languages : en
Pages : 24
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Book Description
In November 1999, the Institute of Medicine, in consultation with the Commission on Life Sciences, the Commission on Physical Sciences, Mathematics, and Applications, and the Board on Science, Technology and Economic Policy launched a one year study on technologies for early detection of breast cancer. The committee was asked to examine technologies under development for early breast cancer detection, and to scrutinize the process of medical technology development, adoption, and dissemination. The committee is gathering information on these topics for its report in a number of ways, including two public workshops that bring in outside expertise. The first workshop on "Developing Technologies for Early Breast Cancer Detection" was held in Washington DC in February 2000. The content of the presentations at the workshop is summarized here. A second workshop, which will focus on the process of technology development and adoption, will be held in Washington, DC on June 19-20. A formal report on these topics, including conclusions and recommendations, will be prepared by the committee upon completion of the one-year study.
Author: Angie Molina Delgado
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Breast cancer is the most common malignancy in women, affecting one out of eight women worldwide. Even if most of the breast tumors are efficiently treated using targeted therapies, there is still a heterogeneous breast cancer subpopulation known as “triple-negative”, which is highly metastatic and, due to the absence of targeted therapies, of poor prognosis. The elucidation of the processes involved in tumor progression and metastasis remains an important challenge in the search for new therapies against this subtype of breast cancer. Previous results from the laboratory have shown that ATIP3, a major product of the candidate tumor suppressor gene MTUS1, is a microtubule associated protein (MAP), whose expression is decreased in 85% of high grade, 83% of triple negative and 62% of metastatic breast carcinomas. Re-expression of ATIP3 in breast cancer cells significantly reduces cell proliferation in vitro, and tumor growth in vivo. Based on these results, my PhD project aimed at evaluating the role of ATIP3 in tumor cell migration and cancer metastasis. In the first part of my thesis, I will present data showing that ATIP3 is a novel prognostic marker for breast cancer patients' survival and a new anti-metastatic molecule. By means of DNA microarray analysis, we showed that low ATIP3 expression levels correlate with reduced overall survival of metastatic breast cancer patients. Using an in vivo model for cancer metastasis, we then showed that re-expression of ATIP3 reduces metastatic progression and lowers the number and size of metastatic foci. At the functional level, ATIP3 reduces breast cancer cell migration by reducing cell velocity and directionality. At the molecular level we further showed, using nocodazole washout experiments and MT growing ends tracking, that ATIP3 slows MT regrowth and decreases MT dynamics. Altogether, these studies indicate that ATIP3 is a novel MT stabilizing protein that controls the ability of MT tips to reach the cell cortex during migration, a mechanism that may account for reduced cell migration and metastasis. In the second part of my thesis, I will present data investigating the mechanisms by which ATIP3 regulates MT dynamics. To this end, we searched for new ATIP3-interacting partners. Interestingly, EB1, the core component of plus-end tracking proteins, was found to interact with ATIP3 not at the growing end of the MTs (as most EB1-interacting proteins), but mostly in the cytosol and at the MT lattice. The identification of the EB1-interacting domain of ATIP3 (termed CN) and further characterization of deletion mutants revealed that ATIP3-EB1 interaction is involved in impaired accumulation of EB1 at the plus-end. Based on these results and on FRAP analysis of EB1-GFP fluorescence recovery, a model was proposed in which the interaction between ATIP3 and EB1 may slower EB1 turnover at the MT plus-end, possibly by limiting EB1 association with its recognition site. In line with this model, in ATIP3-depleted cells dynamic EB1 molecules are more prone to accumulate at the growing end to increase MT dynamics. Relevance of this model in human pathology was then tested by evaluating ATIP3-EB1 expression levels in breast tumors, indicating that combined relative expression levels of both proteins may be considered as a prognostic marker of patient survival. Finally, in a third part of my thesis, I will present some preliminary data showing that ATIP3 may interact with the depolymerizing kinesin MCAK and the tumor suppressor APC, both of which are also well-known partners of EB1. The characterization and the implication of these interactions on ATIP3 functions (MT dynamics for MCAK interaction and cell polarity for APC interaction) remains to be investigated.
Author: Rahul Jandial
Publisher: CRC Press
ISBN: 9781587066597
Category : Medical
Languages : en
Pages : 312
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Book Description
Most cancer deaths are a result of metastasis. The spread of a primary tumor to colonize neighboring and distant organs is the relentless endgame that defines the neoplastic process. Patients who have been diagnosed with cancer are treated to prevent both the recurrence of the tumor at the site of origin and metastasis that would re-stage them as advanced stage IV cancer. Historically and still with some types of cancer, stage IV is perceived by patients as “terminal.” Fortunately, recent molecular therapies have extended the lives of patients with advanced cancer and reassuringly people living with metastatic disease increasingly visit our clinics. What is the path forward? Given that the consilience of science and medicine is a dynamic art from which therapies arise, it would be misguided to consider any single work adequate at capturing the horizon for research. So with humility we constructed this text as primer for scientists. It begins with a broad introduction to the clinical management of common cancers. This is intended to serve as a foundation for investigators to consider when developing basic science hypotheses. Unquestionably, medical and surgical care of cancer patients reveals biology and dictates how novel therapeutics will ultimately be evaluated in clinical trials. The second section of this text offers provocative and evolving insights that underscore the breadth of science involved in the elucidation of cancer metastasis biology. The text concludes with information that integrates scientific and clinical foundations to highlight translational research. This book serves as a framework for scientists to conceptualize clinical and translational knowledge on the complexity of disease that is metastatic cancer.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 141
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The objects of this project are to develop a high-throughput method for screening potential inhibitors of breast cancer cell migration, and to apply this method to identify signaling events mediating constitutive migration of malignant breast cells. The pathways that control these signaling events may be targets for development of new classes of anti-tumor drugs. The significant advances made during this project include (1) development of an efficient, high-throughput migration assay compatible with drug screening; (2) identification of three molecules that are involved in integrin-mediated cell signaling and migration (RACK 1, Focal Adhesion Kinase, and Ca+2); (3) development of a model system for examining integrin-specific signaling in breast cells adhering to laminin-1; and (4) the identification of perillyl alcohol as a non-cytotoxic inhibitor of breast cell migration. The significance of this work is demonstration of the utility of the novel migration inhibitor drug screen we have developed, plus development of reagents that will enable us to examine the signaling associated with specific integrin complexes in breast cells.
Author: Alexander Kiepas
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
"Many physiological processes, including angiogenesis, neurodevelopment and wound healing, rely on the directed movement of cells through the extracellular matrix (ECM). Cell migration is also a fundamental process involved in cancer metastasis. Indeed, proteins that enhance focal adhesion and actin cytoskeletal dynamics are often upregulated in invasive and metastatic cancer cells. In this thesis, we show that the adapter proteins ShcA (p46/52 isoforms) and lipoma-preferred partner (LPP) are required for the migration and invasion of ErbB2-overexpressing breast cancer cells in response to transforming growth factor [beta] (TGF[beta]). Live-cell microscopy techniques reveal that ShcA and LPP are both required for TGF[beta]-enhanced assembly and disassembly of adhesions. Moreover, p46/52ShcA must be phosphorylated on three key tyrosine residues (Y239/Y240/Y313) and LPP must interact with the actin cytoskeleton through its [alpha]-actinin binding domain (ABD) to mediate these effects. Using a BioID proximity labeling approach, we show that p46/52ShcA exists in a complex with various adhesion and actin cytoskeletal proteins, including paxillin and LPP. Total internal reflection fluorescence (TIRF) and 3D super-resolution iPALM microscopy confirm that p46/52ShcA is a novel component of adhesions and its localization to these structures precedes LPP.In addition to acting as a scaffold, the ECM provides biophysical cues that direct cell migration. We demonstrate that LPP is required for ErbB2+ breast cancer cells to sense substrate stiffness. Cells expressing wildtype LPP exhibit enhanced migration rates on intermediate stiffnesses (30-50 kPa), and slower migration rates on soft (10 kPa) and stiff (90kPa) substrates; in contrast, cells lacking LPP expression migrate at a constant speed. ErbB2+ cells also modulate invasive activity based on substrate stiffness. In particular, cells invade maximally on soft (5 kPa) and hard (100 kPa) substrates where migration is significantly reduced. This is the first study to demonstrate that LPP mediates mechanosensitivity in breast cancer cells.Breast cancer is a highly heterogenous disease with considerable cellular, molecular and pathological differences between patients. We find that LPP also plays an important role during TGF[beta]-enhanced migration and invasion of triple-negative breast cancer (TNBC) cells. Human MDA-MB-231 cells with lower levels of LPP expression fail to exhibit TGF[beta]-enhanced migration and invasion. Mouse 4T1 cells, and 4T1 derivatives that preferentially metastasize to the lungs (4T1-526) and live (4T1-2776), also fail to exhibit TGF[beta]-enhanced migration and invasion when LPP expression is reduced. Consequently, 4T1-2776 cells lacking LPP develop fewer liver metastases following splenic injection.Many of experimental results described in this thesis were obtained with live-cell fluorescence microscopy. Fluorescence microscopy provides a convenient, selective and sensitive way to observe live-cell dynamics; however, phototoxicity is a significant limitation of this technique. In this thesis, we show that much of the phototoxicity and photobleaching experienced with live-cell fluorescence imaging occurs as a result of “illumination overhead” (IO). This occurs when a sample is illuminated but fluorescence emission is not being captured by the microscope camera. As a result, we developed a workflow to optimize imaging conditions on any standard microscope. The workflow includes a guide on how to (1) determine the maximum image exposure time for a dynamic process, (2) optimize excitation light intensity, and (3) assess cell health with mitochondrial markers"--
Author: Alecsandru Ioan Baba
Publisher:
ISBN: 9789732714577
Category : Electronic books
Languages : en
Pages : 787
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Author: Romana E. Ranftl
Publisher:
ISBN:
Category :
Languages : en
Pages : 13
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Book Description
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.
Author: Weinberg, Robert A.
Publisher: W.W. Norton & Company
ISBN: 0815345283
Category : Science
Languages : en
Pages : 6
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Book Description
Incorporating the most important advances in the fast-growing field of cancer biology, the text maintains all of its hallmark features. It is admired by students, instructors, researchers, and clinicians around the world for its clear writing, extensive full-color art program, and numerous pedagogical features.
Author: Ajit Varki
Publisher: CSHL Press
ISBN: 9780879696818
Category : Medical
Languages : en
Pages : 694
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Book Description
Sugar chains (glycans) are often attached to proteins and lipids and have multiple roles in the organization and function of all organisms. "Essentials of Glycobiology" describes their biogenesis and function and offers a useful gateway to the understanding of glycans.
