Multifunctional Role of Pancreatic Differentiation 2 PD2 in Pancreatic Cancer

Written By Arokia Priyanka Vaz
Multifunctional Role of Pancreatic Differentiation 2  PD2  in Pancreatic Cancer
  • Publsiher : Unknown
  • Release : 31 July 2021
  • ISBN : 0987654321
  • Pages : 486 pages
  • Rating : 4/5 from 21 reviews
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Read or download book entitled Multifunctional Role of Pancreatic Differentiation 2 PD2 in Pancreatic Cancer written by Arokia Priyanka Vaz which was release on 31 July 2021, this book published by Unknown. Available in PDF, EPUB and Kindle Format. Book excerpt: Cancer is a devastating disease that claims the lives of countless people due to its uncontrolled growth pattern. Among various cancers, pancreatic cancer is one of the most lethal cancers due to its aggressive nature, lack of early symptoms and resistance to chemotherapy. The molecular profile of this deadly malignancy is not completely understood. Malignancy arises due to loss or gain of function in genes involved in cell cycle progression leading to disruption of tightly regulated transitions. In addition the evolving concept of cancer throws light on a small population of cells within the tumor known as the cancer stem cells (CSCs) or tumor-initiating cells that are resistant to all drugs treatment and contributes towards tumor initiation and recurrence. Several studies have been carried out to identify specific markers for the cancer stem cell population including that of pancreatic cancer. Pancreatic Differentiation 2 (PD2) or human Polymerase Associated Factor 1 (hPaf1) is an important component of the multifunctional PAF1 complex initially identified to play a crucial role in transcriptional elongation of genes. During the last decade, several papers on PD2 showed that it is a multifaceted molecule playing roles in cell cycle regulation, stem cell maintenance, histone methylation, chromatin remodeling and acinar-to-ductal metaplasia. In this dissertation, the first goal was to investigate the role of PD2 in pancreatic cancer stem cells. Initially, we analyzed the expression and function of PD2 in pancreatic cancer stem cells isolated from pancreatic cancer cell lines, Kras (G12D); Pdx1 (Cre)(KC), Kras (G12D); Trp53 (R172H/+.); Pdx1(Cre) (KPC) mouse models and human pancreatic tumors. Furthermore, the expression of PD2 was significantly higher in CSCs isolated from pancreatic cancer cells along with CSC markers. These cells were shown to exhibit a cobblestone appearance, increased tumorsphere formation and significant tumor growth, characteristic of the CSC phenotype. interestingly, PD2 was found to be specifically overexpressed in a subpopulation of cells within mouse KC, KPC and human pancreatic tumors, which co-express CSC markers. The drug resistance property was impaired upon knockdown of PD2 with simultaneous alteration in the CSC phenotype and reduction in CD133 and MDR2 gene expression. Overall, my study identified that PD2 has a role in self-renewal and drug resistance of pancreatic CSCs. The second part of my dissertation was primarily focused at exploring the functional role of PD2 in pancreatic cancer cells. The ectopic overexpression of PD2 resulted in increased growth rate of tumor cells both in vitro and in vivo. Overexpression of PD2 led to increased growth, colony formation and migration. Interestingly, elevated expression of PD2 also increased the percentage of CSCs. Furthermore, in vivo studies revealed that PD2 overexpression leads to increased tumor volume and metastasis to distant secondary sites. These results were corroborated at the protein level where elevated expression of PD2 led to the up-regulation of c-Myc which is an important player in tumorigenesis and metastasis. In addition, the expression of PD2 in pancreatic cancer tissues and in vitro pancreatic progression model was elucidated. We demonstrated that the expression of PD2 was increased in the ducts present in the pancreatic cancer tissues when compared to the normal tissues. Likewise, the expression of PD2 was elevated in the transformed Human Pancreatic Nestin expressing (HPNE) cells when compared to the untransformed HPNE cells. Understanding the role of PD2 through cell lines led to my next aim to generate PD2 conditional knockout mice in order to substantiate our earlier work in cancer stem cells and acinar to ductal metaplasia during PC initiation. The animal model would be an important resource for understanding the role of PD2 in detail. Taken together, our findings demonstrate that PD2 is an essential member of the oncogene family that plays a significant role in facilitating drug resistance and cancer stem cell maintenance thereby acting as a positive regulator of cancer.

Multifunctional Role of Pancreatic Differentiation 2 PD2 in Pancreatic Cancer

Multifunctional Role of Pancreatic Differentiation 2  PD2  in Pancreatic Cancer
  • Author : Arokia Priyanka Vaz
  • Publisher : Unknown
  • Release Date : 2015
  • Total pages : 486
  • ISBN : 0987654321
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Summary : Cancer is a devastating disease that claims the lives of countless people due to its uncontrolled growth pattern. Among various cancers, pancreatic cancer is one of the most lethal cancers due to its aggressive nature, lack of early symptoms and resistance to chemotherapy. The molecular profile of this deadly malignancy ...

Stem Cells and Cancer Stem Cells Volume 12

Stem Cells and Cancer Stem Cells  Volume 12
  • Author : M.A. Hayat
  • Publisher : Springer Science & Business Media
  • Release Date : 2014-02-20
  • Total pages : 256
  • ISBN : 0987654321
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Summary : Volume 12 in this series explores the latest experimental and clinical uses of stem cells in the treatment of disease and of injuries and reviews methods for isolating multipotent endothelial-like cells from human adipose tissue and discusses clinical applications in cell therapy and regenerative medicine. The book is organized in five ...

The Pulmonary Neuroepithelial Body Microenvironment

The Pulmonary Neuroepithelial Body Microenvironment
  • Author : Inge Brouns,Line Verckist,Isabel Pintelon,Jean-Pierre Timmermans,Dirk Adriaensen
  • Publisher : Springer Nature
  • Release Date : 2021-05-05
  • Total pages : 99
  • ISBN : 0987654321
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Summary : This monograph sheds new light on pulmonary sensory receptors. Diving into the pulmonary microenvironment, the book focuses on the role of pulmonary neuroepithelial bodies (NEBs) as potential receptors and effectors, able to store and release neurotransmitters. It explores NEBs as potential stem cell niche and highlights the multidisciplinary approach taken ...

Stem Cells and Cancer Stem Cells Volume 13

Stem Cells and Cancer Stem Cells  Volume 13
  • Author : M.A. Hayat
  • Publisher : Springer
  • Release Date : 2015-10-26
  • Total pages : 123
  • ISBN : 0987654321
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Summary : This is the thirteenth volume in a series which presents current understanding of stem cells and cancer stem cells. This book presents many relevant topics including the different sources of cancer stem cells: the features, roles and clinical potential of stem cells emerge from engaging with this comprehensive work. Chapters ...

Stem Cells and Human Diseases

Stem Cells and Human Diseases
  • Author : Rakesh K. Srivastava,Sharmila Shankar
  • Publisher : Springer Science & Business Media
  • Release Date : 2012-02-01
  • Total pages : 630
  • ISBN : 0987654321
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Summary : The main objective of this book is to provide a comprehensive review on stem cells and their role in tissue regeneration, homeostasis and therapy. In addition, the role of cancer stem cells in cancer initiation, progression and drug resistance are discussed. The cell signaling pathways and microRNA regulating stem cell ...

Stem Cells and Cancer Stem Cells Volume 12

Stem Cells and Cancer Stem Cells  Volume 12
  • Author : M.A. Hayat
  • Publisher : Springer
  • Release Date : 2014-03-10
  • Total pages : 256
  • ISBN : 0987654321
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Summary : Volume 12 in this series explores the latest experimental and clinical uses of stem cells in the treatment of disease and of injuries and reviews methods for isolating multipotent endothelial-like cells from human adipose tissue and discusses clinical applications in cell therapy and regenerative medicine. The book is organized in five ...

Multifunctional Nanomaterials for Advanced Molecular Imaging and Cancer Therapy

Multifunctional Nanomaterials for Advanced Molecular Imaging and Cancer Therapy
  • Author : Prasad Subramaniam
  • Publisher : Unknown
  • Release Date : 2014
  • Total pages : 138
  • ISBN : 0987654321
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Summary : Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused ...

Proteoglycans in Stem Cells

Proteoglycans in Stem Cells
  • Author : Martin Götte,Karin Forsberg-Nilsson
  • Publisher : Springer
  • Release Date : 2021-06-08
  • Total pages : 308
  • ISBN : 0987654321
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Summary : This book provides a state-of-the-art compendium on the role of proteoglycans and glycosaminoglycans during development and in cancer. It also suggests directions for novel therapeutic and biotechnological applications in stem cell biology. Proteoglycans and glycosaminoglycans, as part of the extracellular matrix, are multifunctional modulators of growth factor, cytokine, integrin and ...

Stem Cells and Cancer Stem Cells Volume 6

Stem Cells and Cancer Stem Cells  Volume 6
  • Author : M.A. Hayat
  • Publisher : Springer Science & Business Media
  • Release Date : 2012-02-27
  • Total pages : 448
  • ISBN : 0987654321
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Summary : The difference among pluripotent stem cells, multipotent stem cells, and unipotent stem cells is pointed out. Vast therapeutic applications of the following specific stem cells in disease and tissue injury are discussed: human embryonic stem cells, human mesenchymal stem cells, germ cell-derived pluripotent stem cells, induced pluripotent stem cells, human ...

Stem Cells as Targeted Drug Delivery Vehicles

Stem Cells as Targeted Drug Delivery Vehicles
  • Author : Rebecca Lim,Jessica E. Frith,Gina D. Kusuma,Christopher G. Sobey
  • Publisher : Frontiers Media SA
  • Release Date : 2021-02-03
  • Total pages : 212
  • ISBN : 0987654321
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Summary : Topic Editor RL is a patent inventor on exosome-related patents, PCT/AU2017/050821 and PCT/AU2016/050468. All other Topic Editors declare no competing interests with regards to the Research Topic subject....

Stem Cells and Cancer Stem Cells Volume 3

Stem Cells and Cancer Stem Cells Volume 3
  • Author : M.A. Hayat
  • Publisher : Springer Science & Business Media
  • Release Date : 2011-11-22
  • Total pages : 400
  • ISBN : 0987654321
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Summary : It is pointed out that cancer stem cell is a cell type within a tumor that possesses the capacity of cell-renewal and can give rise to the heterogeneous lineages of cancer cells that comprise the tumor. It is emphasized that a cancer stem cell is a tumor initiating cell. That ...

Forum

Forum
  • Author : Anonim
  • Publisher : Unknown
  • Release Date : 1997
  • Total pages : 212
  • ISBN : 0987654321
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Summary : Download or read online Forum written by , published by which was released on 1997. Get Forum Books now! Available in PDF, ePub and Kindle....

The Mast Cell

The Mast Cell
  • Author : Domenico Ribatti
  • Publisher : Springer
  • Release Date : 2019-07-11
  • Total pages : 112
  • ISBN : 0987654321
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Summary : Mast cells (MC) are phylogenetically old cells which are distributed throughout the human organism. MC are found in almost all of the major organs and tissues of the body, particularly in association with connective tissue structures such as blood vessels, lymphatic vessels and nerves, and in proximity to surfaces that ...

Stem Cells and Cancer Stem Cells Volume 7

Stem Cells and Cancer Stem Cells  Volume 7
  • Author : M.A. Hayat
  • Publisher : Springer Science & Business Media
  • Release Date : 2012-06-12
  • Total pages : 278
  • ISBN : 0987654321
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Summary : The seventh in Springer’s landmark series of edited volumes on one of the highest-profile subjects in contemporary medicine and scientific endeavour, this volume sets out to cover a staggering range of research into the medical applications of stem cell research. While stem cells are the very stuff of life ...

Stem Cells in Development and Disease

Stem Cells in Development and Disease
  • Author : Anonim
  • Publisher : Academic Press
  • Release Date : 2014-01-15
  • Total pages : 472
  • ISBN : 0987654321
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Summary : This new volume of Current Topics in Developmental Biology covers Stem Cells in Development and Disease. The chapters provide a comprehensive set of reviews covering such topics as the mechanisms of pluripotency in vivo and in vitro, hematopoietic stem cell development, intestinal stem cells and their defining niche, epithelial stem ...