Energy Balance and Cancer

Series Editor:Nathan A. BergerCase Western Reserve UniversityCleveland, OH, USA

For further volumes:http://www.springer.com/series/8282

Nathan A. BergerEditor

Murine Models, Energy Balance, and Cancer

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ISSN 2199-2622 ISSN 2199-2630 (electronic)Energy Balance and CancerISBN 978-3-319-16732-9 ISBN 978-3-319-16733-6 (eBook)DOI 10.1007/978-3-319-16733-6

Library of Congress Control Number: 2015940548

Springer Cham Heidelberg New York Dordrecht London© Springer International Publishing Switzerland 2015This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recita-tion, broadcasting, reproduction on microfilms or in any other physical way, and transmission or in-formation storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publica-tion does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made.

Printed on acid-free paper

Springer International Publishing AG Switzerland is part of Springer Science+Business Media(www.springer.com)

EditorNathan A. BergerCenter for Science, Health & SocietyCase Western Reserve University School of MedicineCleveland, OhioUSA

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Preface

Overweight and obesity have increased on a worldwide basis, reaching 60–70 % of the adult population in developed countries and the incidence continues to increase in developing countries. In addition to having devastating psychosocial impact and causing severe debilitation and death at the individual level, this obesity pandemic along with an associated increase in multiple malignancies poses a major series of public health problems that challenge both health care systems and health care costs. Cohort and case control studies in humans have contributed significantly to under-standing the epidemiology and clinical correlates of these problems. Likewise, great insights have been gained from biochemical, molecular biologic, genetic, physio-logic, and pathologic analysis of human tissues and fluids, and in some cases, it has been possible to conduct randomized controlled trials in humans to study cause and control. The latter, however, have usually been short-term relative to the long-term problems of obesity development and control and its relation to cancer. Moreover, obesity and its comorbidities have been difficult to study in humans due to difficul-ties in sustaining controlled diets, environments, and behavior modifications as well as ethical and technical considerations that preclude performance of human experi-ments where harmful effects such as the development of obesity and/or cancer may be an important component of the endpoint.

In contrast to the research limitations imposed by human studies, animal studies offer many advantages, and murine systems have been particularly useful to study the relation of cancer with diet, obesity, and other factors affecting energy balance. These models are useful, first because rodents are similar to humans in that they develop a series of diseases characteristic of humans including diabetes, hyper-tension, obesity, cardiovascular disease, autoimmune disorders, and a variety of malignancies including carcinomas, sarcomas, lymphomas, and leukemias. In ad-dition, they are small, easy to handle, easy to control, and manipulate their diet and environment. Another important attribute of murine models is that a series of immu-nodefficient strains, athymic “nude” mice, and severe combined immunodefficient (SCID) mice, lacking major components of the immune system are available, which make it easy to transplant tumors as pieces, minces, or cell suspensions, between animals or from tumor cell lines and across species, including from humans to mice, to study the consequences of variations in energy balance such as diet and exercise.

vi Preface

Transplanted tumors are useful also for the studies of new therapeutic agents alone and in combination.

Like that of humans, the entire mouse genome has been sequenced and areas of similarity and differences can be compared. The ability to develop inbred strains of mice provides the basis for statistically significant genetic and phenotypic ex-pression of normal and abnormal traits and their association with specific genes and their products. Moreover, the ability to genetically modify mice by making transgenic, knockout, knockin, and consomic chromosome animals, provides the basis for developing a variety of sophisticated and valuable tools to elucidate the independent and combined contributions of specific factors to the obesity–cancer relation. In addition, their short reproduction time makes it easy to study both ge-netic and epigenetic influences. The value of these models is further enhanced by technology to identify DNA sequence changes that result in cancer driver genes in humans and then reproduce them in mice to study the interaction of obesity with a variety of other genetic, epigenetic, and environmental modifiers such as diet, exer-cise, diurnal rhythm, and others on cancer. Likewise, a series of devices including tread mills, running wheels, swimming apparatus, and motion detectors have been developed for mice to encourage and provide opportunities for exercise, exercise training, and measurement of physical activity, endurance, and energy consumption.

This volume in the Energy Balance and Cancer series discusses many of the leading murine models used to study the mechanisms and markers linking obesity to cancer, their modification by environment, and how they may continue to be used to further elucidate these relations and explore preclinical aspects of prevention and/or therapeutic interventions.

In Chap. 1, Luciano DiTacchio and Kacee A. DiTacchio (University of Kansas) and Satchidananda Panda (Salk Institute for Biological Sciences) discuss the use of murine models to study the relevance of normal and disrupted circadian rhythm in cancer. In Chap. 2, Lei Cao (Ohio State University) examines the dramatic ef-fect of environmental manipulation and consequent alterations in neuropeptides as mediators of the impact of energy balance and cancer. Ellen Heber-Katz (Wistar Institute) and Robert Naviaux (University of California San Diego), in Chap. 3, discuss the MRL mouse model of regeneration and cancer, while in Chap. 4, Dar-lene Berryman, Vivian Lesende, Lara Householder, Edward List, John Kopchick (Ohio University) discuss mouse lines with altered growth hormone secretion af-fecting fat metabolism and cancer. In Chap. 5, Jonathan Tucci and Steven Mittel-man (University of Southern California) discuss mouse models to study hemato-logic malignancies, while in Chap. 6, Stephen Hursting, Emily Rossi, Laura Bow-ers (University of North Carolina at Chapel Hill), and Laura Lashinger (University of Texas at Austin) summarize lessons learned from genetically engineered mice to study the effect of insulin-like growth factor (IGF)-1 on energy balance and can-cer. Praveena Thiagarajan and Ofer Reizes (Cleveland Clinic) report, in Chap. 6, the exciting use of murine models to study leptin effects in breast cancer stem cells. In Chap. 8, Zara Zelenko, Derek LeRoith, and Emily Gallagher (Ican School of Medicine at Mount Sinai) discuss the use of murine models to study the interre-lated effects of diabetes, insulin, and IGFs on cancer. In Chap. 9, Henry Thompson

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(Colorado State University) provides a conceptually challenging discussion of the impact of energy balance on chemically induced mammary carcinogenesis in the rat. Hui-Hua Chang, Guido Eibl, and Enrique Rozengurt (David Geffen School of Medicine at University of California Los Angeles) discuss the recent advances in mouse models to study the effects of energy balance on pancreatic cancer in Chap. 10. Chapter 11, by Emily Benesh and Kelle Moley (Washington University) provides an interesting epigenetic examination of how maternal energy balance af-fects prostate cancer in offspring. Dipali Sharma (Johns Hopkins University) and Neeraj Saxena (University of Maryland), in Chap. 12, provide a comprehensive review of mouse models to study the nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and hepatocellular carcinoma and the effect of natural product. In Chap. 13, Abraham Schneider (University of Maryland) provides an important ex-amination of the use of mouse models to study metformin in carcinogenesis.

Overall, this volume provides a series of diverse murine models for studying many of the malignancies affected by energy balance in humans and a variety of techniques by which these studies may be approached. The volume should be of high interest to all the investigators concerned with the relations between energy balance and cancer, and serve as a useful guide to those interested in performing controlled research in model systems relative to these processes.

Cleveland, Ohio Nathan A. Berger

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Contents

1 Relevance of Circadian Rhythm in Cancer ............................................ 1Luciano DiTacchio, Kacee A. DiTacchio and Satchidananda Panda

2 Environmental Manipulation and Neuropeptide Effects on Energy Balance and Cancer ..................................................................... 21Lei Cao

3 The MRL Mouse: A Model of Regeneration and Cancer ...................... 47Ellen Heber-Katz and Robert K. Naviaux

4 Living Large: What Mouse Models Reveal about Growth Hormone and Obesity ............................................................................... 65Darlene E. Berryman, Lara Householder, Vivian Lesende, Edward O. List and John J. Kopchick

5 Mouse Models to Study Obesity Effects on Hematologic Malignancies .................................................................. 97Jonathan Tucci and Steven D. Mittelman

6 Energy Balance, IGF-1, and Cancer: Causal Lessons from Genetically Engineered Mice ................................................................... 117Stephen D. Hursting, Emily L. Rossi, Laura W. Bowers and Laura M. Lashinger

7 Mouse Models to Study Leptin in Breast Cancer Stem Cells ............... 127Praveena S. Thiagarajan and Ofer Reizes

8 Mouse Models Used to Study the Effects of Diabetes, Insulin, and IGFs on Cancer .................................................................................. 153Zara Zelenko, Derek LeRoith and Emily J. Gallagher

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9 Impact of Energy Balance on Chemically Induced Mammary Carcinogenesis in a Rat ......................................................... 175Henry J. Thompson

10 Models and Mechanisms of High-Fat Diet (HFD) Promotion of Pancreatic Cancer ................................................................................. 197Hui-Hua Chang, Guido Eibl and Enrique Rozengurt

11 Maternal Energetics and the Developmental Origins of Prostate Cancer in Offspring ................................................................... 217Emily C. Benesh and Kelle H. Moley

12 Mouse Models to Study the Effect of Natural Products on Obesity-Associated NAFLD/NASH .................................................... 247Dipali Sharma and Neeraj K. Saxena

13 Mouse Models to Study Metformin Effects in Carcinogenesis ............. 271Abraham Schneider

Index ................................................................................................................. 293

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About the Editor

Nathan A. Berger is a Distinguished University Professor. He is the Hanna-Payne Professor of experimental medicine, and the Director of the Center for Science, Health, and Society. He is Professor of medicine, biochemistry, genetics, and on-cology at Case Western Reserve University, School of Medicine. He is a member of many professional societies, including the American Society of Hematology, the American Society for Biochemistry and Molecular Biology, the American Society of Clinical Oncology, the American Association for Cancer Research, the American Society of Clinical Investigation, and the Association of American Physicians. Dr. Berger, who serves on many national peer review panels and committees for the National Cancer Institute, has published over 200 scientific papers, which have re-ceived 5,443 citations.

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Contributors

Emily C. Benesh Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA

Darlene E. Berryman Edison Biotechnology Institute, Ohio University, Athens, OH, USA; School of Applied Health Sciences and Wellness, College of Health Sciences and Professions, Ohio University, Athens, OH, USA; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Konneker Research Laboratories, Ohio University, Athens, OH, USA

Laura W. Bowers Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Lei Cao College of Medicine, The Ohio State University, Columbus, OH, USA

Hui-Hua Chang Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Kacee A. DiTacchio Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA

Luciano DiTacchio Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA

Guido Eibl Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; CURE: Digestive Diseases Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

Emily J. Gallagher Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, New York, One Gustave L. Levy PlaceNY, USA

Ellen Heber-Katz The Wistar Institute, Philadelphia, PA, USA

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Lara Householder Edison Biotechnology Institute, Ohio University, Athens, OH, USA; School of Applied Health Sciences and Wellness, College of Health Sciences and Professions, Ohio University, Athens, OH, USA; Konneker Research Laboratories, Ohio University, Athens, OH, USA

Stephen D. Hursting Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

John J. Kopchick Edison Biotechnology Institute, Ohio University, Athens, OH, USA; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Konneker Research Laboratories, Ohio University, Athens, OH, USA

Laura M. Lashinger Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA

Derek LeRoith Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, New York, One Gustave L. Levy PlaceNY, USA

Vivian Lesende Edison Biotechnology Institute, Ohio University, Athens, OH, USA; Konneker Research Laboratories, Ohio University, Athens, OH, USA

Edward O. List Edison Biotechnology Institute, Ohio University, Athens, OH, USA; Konneker Research Laboratories, Ohio University, Athens, OH, USA

Steven D. Mittelman Departments of Pediatrics and Physiology & Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Kelle H. Moley James P. Crane Professor, Department of Obstetrics and Gynecology, Washington University in Saint Louis, School of Medicine, Saint Louis, MO, USA

Robert K. Naviaux UCSD School of Medicine, San Diego, CA, USA

Satchidananda Panda Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA

Ofer Reizes Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

Emily L. Rossi Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Enrique Rozengurt Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; CURE: Digestive Diseases Research Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

xvContributors

Neeraj K. Saxena Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

Abraham Schneider School of Dentistry, Department of Oncology and Diagnostic Sciences, University of Maryland, Baltimore, MD, USA

Dipali Sharma Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Praveena S. Thiagarajan Department of Cellular & Molecular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA

Henry J. Thompson Cancer Prevention Laboratory, Colorado State University, Fort Collins, CO, USA

Jonathan Tucci Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

Zara Zelenko Division of Endocrinology, Diabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, New York, One Gustave L. Levy PlaceNY, USA