Mouse Models of Cancer: Methods and Protocols

460 Pages·2015·19.087 MB·English

by  Robert Eferl, Emilio Casanova (eds.)

Methods in
Molecular Biology 1267
Robert Eferl
Emilio Casanova Editors
Mouse Models
of Cancer
Methods and Protocols
M M B
ETHODS IN OLECULAR IOLOGY
Series Editor
John M. Walker
School of Life and Medical Sciences
University of Hertfordshire
Hat fi eld, Hertfordshire, AL10 9AB, UK
For further volumes:
h ttp://www.springer.com/series/7651

Mouse Models of Cancer
Methods and Protocols
Edited by
Robert Eferl
Medical University Vienna (MUV), Institute of Cancer Research, Vienna, Austria
Emilio Casanova
Medical University Vienna (MUV), Center of Physiology and Pharmacology & Ludwig Boltzmann
Institute for Cancer Research (LBI-CR), Vienna, Austria
Editors
Robert E ferl Emilio C asanova
Medical University Vienna (MUV) Medical University Vienna (MUV)
Institute of Cancer Research Center of Physiology and Pharmacology &
Vienna, Austria Ludwig Boltzmann Institute for Cancer
Research (LBI-CR)
Vienna, Austria
ISSN 1064-3745 ISSN 1940-6029 (electronic)
ISBN 978-1-4939-2296-3 ISBN 978-1-4939-2297-0 (eBook)
DOI 10.1007/978-1-4939-2297-0
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Prefa ce
This book is dedicated to geneticists, molecular biologists, biochemists, and medical doc-
tors interested in the use of mouse models in cancer research. Their use as cancer models
has provided exceptional insight into the biology and genetics of human cancers. Mice have
consistent disease manifestations, have good-sized litters of offspring, and are easy to han-
dle, even genetically, some features that have brought the attention of cancer researchers for
decades. Genome sequencing of mice has revealed the extent of genomic similarity with
other mammals including humans. These genomic studies, together with the exquisite
refi nement in genetic engineering techniques, have greatly increased the value of mouse
models for research on cancer and many other human disorders.
Despite their broad use in cancer research, a certain amount of skepticism about their
value and relevance for human cancer is present in the scientifi c and clinical community.
This is likely due to the differences between mice and humans, but also to the fact that most
clinical trials still fail despite the use of mouse models in the preceding discovery research
phases. Scientists are aware that mouse models need to be further refi ned, and the chapters
in this book offer an updated view to the way this optimization needs to be made. Given
the increasing number of models for different cancers, the fi rst chapters in the book discuss
the best approaches for the use of mouse models in specifi c tumor types of clinical rele-
vance. The second part of the book discusses robust technologies that facilitate in vivo
imaging to track both primary and metastatic tumor development from much earlier stages
than previously possible. These models are able to more accurately model sporadic human
cancers by specifi cally controlling timing and location of mutations, even within single cells,
and by improving the characterization of the phenotype induced by these mutations in liv-
ing mice. Undoubtedly, these sophisticated mouse models will fuel our understanding of
cancer initiation, immune system roles, tumor angiogenesis, invasion, and metastasis, and
the relevance of molecular diversity observed among human cancers.
Finally, we need to remember that mouse models are just that, models. They are
intended to complement, not replace, studies done in humans. However, these models
offer u nique opportunities to investigate cancer mechanisms and optimize drugs in pre-,
co-, and postclinical trials. This manual is therefore a valuable laboratory resource for all
researchers, from the graduate level upwards, who study cancer and new possibilities for
its treatment.
Madrid, Spain M arcos Malumbres
v

Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i x
PART I BACKGROUND
1 Modeling Cancer Using Genetically Engineered Mice. . . . . . . . . . . . . . . . . . . 3
Patricia Stiedl , Beatrice Grabner , Katalin Zboray , Edith Bogner ,
and Emilio Casanova
2 Lung Adenocarcinomas: Comparison Between Mice and Men. . . . . . . . . . . . . 1 9
Helmut H. P opper
PART II INDIVIDUAL CANCERS
3 Mouse Models of Breast Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 7
Kazuhito S akamoto , J effrey W. Schmidt , and K ay-Uwe Wagner
4 G enetically Engineered Mouse Models to Study Prostate Cancer. . . . . . . . . . . 7 3
Elspeth A. Brzezinska , C olin Nixon , Rachana P atel , and Hing Y . Leung
5 P ractical Use of Advanced Mouse Models for Lung Cancer. . . . . . . . . . . . . . . 9 3
Roghaiyeh S afari and R alph M euwissen
6 G eneration and Analysis of Mouse Intestinal Tumors
and Organoids Harboring APC and K-Ras Mutations. . . . . . . . . . . . . . . . . . . 125
Johan H. van Es and Hans C levers
7 Induction of Colorectal Cancer in Mice and Histomorphometric
Evaluation of Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 45
Ilija C rncec , Paulina Pathria , J asmin S vinka , and Robert Eferl
8 Mouse Models of Liver Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 65
Jorge Matias C aviglia and R obert F . S chwabe
9 C urrent Methods in Mouse Models of Pancreatic Cancer . . . . . . . . . . . . . . . . 1 85
Pawel K . M azur , Alexander H erner , Florian N eff , and Jens T. Siveke
10 Mouse Models of Nonmelanoma Skin Cancer. . . . . . . . . . . . . . . . . . . . . . . . . 217
Nicole A mberg , Martin Holcmann , E lisabeth Glitzner ,
Philipp N ovoszel , Gabriel S tulnig , and Maria Sibilia
11 Clinicopathological Characterization of Mouse Models of Melanoma . . . . . . . 2 51
Blake Ferguson , H . P eter S oyer , and G raeme J . Walker
12 Modeling BCR/ABL-Driven Malignancies in the Mouse . . . . . . . . . . . . . . . . 2 63
Christine Schneckenleithner , A ndrea H oelbl-Kovacic , and Veronika S exl
13 Methods to Generate Genetically Engineered Mouse Models
of Soft Tissue Sarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 83
Rebecca D. Dodd , Leonor A ñó , Jordan M . Blum , Zhizhong L i ,
David Van Mater , and David G . Kirsch
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viii Contents
14 Characterization of Mouse Model-Derived Osteosarcoma (OS) Cells
In Vitro and In Vivo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
Özge Uluçkan , Latifa Bakiri , and Erwin F . W agner
15 Genetically Engineered Mouse and Orthotopic Human Tumor
Xenograft Models of Retinoblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 07
Claudia A . B enavente and Michael A . D yer
PART III SPECIFIC ASPECTS
16 Tumor Imaging Technologies in Mouse Models . . . . . . . . . . . . . . . . . . . . . . . 3 21
Michael Bouvet and Robert M. H offman
17 T umor Angiogenesis: Methods to Analyze Tumor Vasculature
and Vessel Normalization in Mouse Models of Cancer. . . . . . . . . . . . . . . . . . . 349
Federica Maione and Enrico Giraudo
18 T ransplantable Mouse Tumor Models of Breast Cancer Metastasis. . . . . . . . . . 3 67
Rumela Chakrabarti and Y ibin K ang
19 M ethods to Study Primary Tumor Cells and Residual Tumor Cells
in Mouse Models of Oncogene Dependence. . . . . . . . . . . . . . . . . . . . . . . . . . 381
Caroline Botta , C edric D arini , Guillaume Darrasse-Jèze ,
and Katrina P odsypanina
20 Generation of Transgenic Mouse Model Using PTTG as an Oncogene . . . . . . 395
Sham S. Kakar and Cohin K akar
21 Modeling the Study of DNA Damage Responses in Mice . . . . . . . . . . . . . . . . 4 13
Julia S pecks , Maria N ieto-Soler , Andres J . Lopez-Contreras ,
and Oscar F ernandez-Capetillo
22 Methods to Study Tumor Surveillance Using Tumor Cell
Transplantation into Genetically Engineered Mice. . . . . . . . . . . . . . . . . . . . . . 4 39
Eva Bauer , A gnieszka Witalisz , Birgit S trobl , and Dagmar Stoiber
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 57
Contributors
NICOLE A MBERG • Department of Medicine I, Institute of Cancer Research, Comprehensive
Cancer Center , M edical University of Vienna , Vienna, A ustria
LEONOR AÑÓ • Duke University Medical Center , D urham, NC, U SA
LATIFA B AKIRI • BBVA Foundation—CNIO Cancer Cell Biology Program , Spanish National
Cancer Research Centre (CNIO) , M adrid, Spain
EVA B AUER • Ludwig Boltzmann Institute for Cancer Research , V ienna, Austria
CLAUDIA A. BENAVENTE • Department of Chemical Biology and Therapeutics,
St. Jude Children’s Research Hospital , Memphis, T N , U SA
JORDAN M. BLUM • Duke University Medical Center , D urham , N C, U SA
EDITH B OGNER • Ludwig Boltzmann Institute for Cancer Research (LBI-CR) , V ienna, Austria
CAROLINE BOTTA • Département de Biologie, U niversité de Lyon, Lyon , F rance
MICHAEL BOUVET • Department of Surgery, Moores Cancer Center, U niversity of
California-San Diego , La Jolla, CA , USA
ELSPETH A. B RZEZINSKA • The Beatson Institute for Cancer Research , G lasgow, UK
EMILIO C ASANOVA • Ludwig Boltzmann Institute for Cancer Research (LBI-CR) , V ienna,
Austria ; C enter of Physiology and Pharmacology, Comprehensive Cancer Center, Institute
of Pharmacology, M edical University of Vienna , V ienna, Austria
JORGE M ATIAS C AVIGLIA • Department of Medicine, C olumbia University , N ew York , NY, USA
RUMELA C HAKRABARTI • Department of Molecular Biology , P rinceton University , P rinceton,
NJ , U SA
HANS CLEVERS • Hubrecht Institute-KNAW , University Medical Center Utrecht , U trecht,
The Netherlands
ILIJA CRNCEC • Institute of Cancer Research (ICR) & Comprehensive Cancer Center
(CCC), M edical University of Vienna , V ienna, A ustria
CEDRIC DARINI • Institut de Recherches Cliniques de Montréal , M ontreal , Q C , Canada
GUILLAUME D ARRASSE-JÈZE • Sorbonne Paris Cité, Faculté de Médecine, Université Paris
Descartes , P aris , F rance ; U1151 UMRS8253, I nstitut Necker Enfants Malades , P aris , France
REBECCA D . DODD • Duke University Medical Center , D urham, NC, U SA
MICHAEL A. DYER • Department of Chemical Biology and Therapeutics , S t. Jude Children’s
Research Hospital , M emphis , T N , U SA
ROBERT EFERL • Institute of Cancer Research (ICR) & Comprehensive Cancer Center
(CCC), Medical University of Vienna , V ienna, A ustria
JOHAN H. V AN ES • Hubrecht Institute-KNAW , U niversity Medical Center Utrecht ,
Utrecht , T he Netherlands
BLAKE FERGUSON • Queensland Institute of Medical Research , Herston, Queensland,
Australia
OSCAR FERNANDEZ-CAPETILLO • Genomic Instability Group, S panish National Cancer
Research Center (CNIO) , Madrid, Spain
ENRICO GIRAUDO • Laboratory of Transgenic Mouse Models, Candiolo Cancer Institute—FPO,
IRCCS , C andiolo, Italy ; Department of Science and Drug Technology , University of Torino ,
Torino, I taly
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