Cancer Contents Research · 2428 Proteomic Portrait of Human Breast Cancer Progression Identifies...
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BREAKING ADVANCES 2157 Highlights from Recent Cancer Literature REVIEWS 2159 The Next Challenge in Cancer Immunotherapy: Controlling T-Cell Traffic to the Tumor Jean-Pierre Abastado 2162 T-Regulatory Cells: Key Players in Tumor Immune Escape and Angiogenesis Andrea Facciabene, Gregory T. Motz, and George Coukos MEETING REPORT 2172 Systems Biology of Tumor Dormancy: Linking Biology and Mathematics on Multiple Scales to Improve Cancer Therapy Heiko Enderling, Philip Hahnfeldt, Lynn Hlatky, and Nava Almog PRIORITY REPORTS 2176 Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100 Juliet Richards, Ai Chiin Lim, Colin W. Hay, Angela E. Taylor, Anna Wingate, Karolina Nowakowska, Carmel Pezaro, Suzanne Carreira, Jane Goodall, Wiebke Arlt, Iain J. McEwan, Johann S. de Bono, and Gerhardt Attard Pr ecis: The administration of corticoid drugs intended to reduce the side effects of abiraterone in the treatment of castration-resistant prostate cancer can actually lead to disease progression via activation of wild-type or mutant androgen receptor. 2183 Bone Marrow Stromal Cells Create a Permissive Microenvironment for Myeloma Development: A New Stromal Role for Wnt Inhibitor Dkk1 Jessica A. Fowler, Gregory R. Mundy, Seint T. Lwin, and Claire M. Edwards Pr ecis: Findings define a pivotal role for the Wnt inhibitor Dkk1 in the stromal cells of the bone marrow microenvironment, which supports development of deadly myeloma blood tumors. 2190 CD73-Deficient Mice Are Resistant to Carcinogenesis John Stagg, Paul A. Beavis, Upulie Divisekera, Mira C.P. Liu, Andreas M€ oller, Phillip K. Darcy, and Mark J. Smyth Pr ecis: This important study offers a preclinical genetic and pharmacologic validation of CD73, a cell-surface enzyme that generates the immune- suppressive nucleoside adenosine, as a critical contributor to immune escape during tumorigenesis and a tractable therapeutic target. CLINICAL STUDIES 2197 Epigenetic Resensitization to Platinum in Ovarian Cancer Daniela Matei, Fang Fang, Changyu Shen, Jeanne Schilder, Alesha Arnold, Yan Zeng, William A. Berry, Tim Huang, and Kenneth P. Nephew Pr ecis: Findings of this phase II clinical trial support the use of DNA methylation-based epigenetic therapies to resensitize drug-resistant tumors to cytotoxic chemotherapy, addressing one of the most important challenges in the oncology clinic. 2206 A RASSF1A Polymorphism Restricts p53/p73 Activation and Associates with Poor Survival and Accelerated Age of Onset of Soft Tissue Sarcoma Karen S. Yee, Lukasz Grochola, Garth Hamilton, Anna Grawenda, Elisabeth E. Bond, Helge Taubert, Peter Wurl, Gareth L. Bond, and Eric O'Neill Pr ecis: This study provides a mechanistic description of a coding SNP in the Ras family member RASSF1A that correlates with survival and onset of disease in soft-tissue sarcoma patients, offering a simple host prognostic marker in this setting. INTEGRATED SYSTEMS AND TECHNOLOGIES 2218 Reconsidering the Paradigm of Cancer Immunotherapy by Computationally Aided Real-time Personalization Yuri Kogan, Karin Halevi–Tobias, Moran Elishmereni, Stanimir Vuk-Pavlovi c, and Zvia Agur Pr ecis: It may be possible to personalize cancer immunotherapy and immunochemotherapy based on mathematical models that are validated early in the treatment process, thereby enabling an adaptive personalized regimen during the treatment period. Contents Cancer Research May 1, 2012 Volume 72 Number 9 A Journal of the American Association for Cancer Research iii www.aacrjournals.org on August 18, 2021. © 2012 American Association for Cancer Research. cancerres.aacrjournals.org Downloaded from
Transcript of Cancer Contents Research · 2428 Proteomic Portrait of Human Breast Cancer Progression Identifies...
BREAKING ADVANCES
2157 Highlights from Recent CancerLiterature
REVIEWS
2159 The Next Challenge in CancerImmunotherapy: ControllingT-Cell Traffic to the TumorJean-Pierre Abastado
2162 T-Regulatory Cells: Key Playersin Tumor Immune Escape andAngiogenesisAndrea Facciabene, Gregory T. Motz, andGeorge Coukos
MEETING REPORT
2172 Systems Biology of Tumor Dormancy:Linking Biology and Mathematics onMultiple Scales to Improve CancerTherapyHeiko Enderling, Philip Hahnfeldt, Lynn Hlatky,and Nava Almog
PRIORITY REPORTS
2176 Interactions of Abiraterone,Eplerenone, and Prednisolone withWild-type and Mutant AndrogenReceptor: A Rationale for IncreasingAbiraterone Exposure or Combiningwith MDV3100Juliet Richards, Ai Chiin Lim, Colin W. Hay,Angela E. Taylor, Anna Wingate,Karolina Nowakowska, Carmel Pezaro,Suzanne Carreira, Jane Goodall, Wiebke Arlt,Iain J. McEwan, Johann S. de Bono, andGerhardt Attard
Pr�ecis: The administration of corticoid drugsintended to reduce the side effects of abiraterone inthe treatment of castration-resistant prostatecancer can actually lead to disease progression viaactivation of wild-type or mutant androgenreceptor.
2183 Bone Marrow Stromal Cells Create aPermissive Microenvironment forMyeloma Development: A NewStromal Role for Wnt Inhibitor Dkk1Jessica A. Fowler, Gregory R. Mundy,Seint T. Lwin, and Claire M. Edwards
Pr�ecis: Findings define a pivotal role for the Wntinhibitor Dkk1 in the stromal cells of the bonemarrow microenvironment, which supportsdevelopment of deadly myeloma blood tumors.
2190 CD73-Deficient Mice Are Resistantto CarcinogenesisJohn Stagg, Paul A. Beavis, Upulie Divisekera,Mira C.P. Liu, Andreas M€oller, Phillip K. Darcy,and Mark J. Smyth
Pr�ecis: This important study offers a preclinicalgenetic and pharmacologic validation of CD73, acell-surface enzyme that generates the immune-suppressive nucleoside adenosine, as a criticalcontributor to immune escape during tumorigenesisand a tractable therapeutic target.
CLINICAL STUDIES
2197 Epigenetic Resensitization to Platinumin Ovarian CancerDaniela Matei, Fang Fang, Changyu Shen,Jeanne Schilder, Alesha Arnold, Yan Zeng,William A. Berry, Tim Huang, andKenneth P. Nephew
Pr�ecis: Findings of this phase II clinical trialsupport the use of DNA methylation-basedepigenetic therapies to resensitize drug-resistanttumors to cytotoxic chemotherapy, addressing oneof the most important challenges in the oncologyclinic.
2206 A RASSF1A Polymorphism Restrictsp53/p73 Activation and Associates withPoor Survival and Accelerated Age ofOnset of Soft Tissue SarcomaKaren S. Yee, Lukasz Grochola, Garth Hamilton,Anna Grawenda, Elisabeth E. Bond,Helge Taubert, Peter Wurl, Gareth L. Bond,and Eric O'Neill
Pr�ecis: This study provides a mechanisticdescription of a coding SNP in the Ras familymember RASSF1A that correlates with survival andonset of disease in soft-tissue sarcoma patients,offering a simple host prognostic marker in thissetting.
INTEGRATED SYSTEMS ANDTECHNOLOGIES
2218 Reconsidering the Paradigm of CancerImmunotherapy by ComputationallyAided Real-time PersonalizationYuri Kogan, Karin Halevi–Tobias,Moran Elishmereni, Stanimir Vuk-Pavlovi�c, andZvia Agur
Pr�ecis: It may be possible to personalize cancerimmunotherapy and immunochemotherapy basedon mathematical models that are validated early inthe treatment process, thereby enabling an adaptivepersonalized regimen during the treatment period.
ContentsCancerResearchMay 1, 2012 � Volume 72 � Number 9
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MICROENVIRONMENT AND IMMUNOLOGY
2228 A Galectin-3–Dependent PathwayUpregulates Interleukin-6 in theMicroenvironment of HumanNeuroblastomaAyaka M. Silverman, Rie Nakata,Hiroyuki Shimada, Richard Sposto, andYves A. DeClerck
Pr�ecis: This study reveals that a regulator ofimmune escape in the tumor microenvironmentregulates the proinflammatory cytokine IL-6, apivotal modifier of cancer progression.
2239 Tumor Angiogenesis Mediated byMyeloid Cells Is Negatively Regulatedby CEACAM1Rongze Lu, Maciej Kujawski, Hao Pan, andJohn E. Shively
Pr�ecis: A cell-surface receptor on myeloid cellsthat inhibits tumor growth is found to restrictproduction of a proangiogenic growth factor thatpromotes the growth of the tumor vasculature.
2251 Chromatin Remodeling Underlies theSenescence-Associated SecretoryPhenotype of Tumor StromalFibroblasts That Supports CancerProgressionErmira Pazolli, Elise Alspach,Agnieszka Milczarek, Julie Prior,David Piwnica-Worms, and Sheila A. Stewart
Pr�ecis: A significant part of the risk provided byaging in cancer may be derived from thecontributions of senescesing stromal fibroblaststhat fuel malignant progression through at least 2independent signaling cascades activated inresponse to chromatin changes.
MOLECULAR AND CELLULARPATHOBIOLOGY
2262 Genetic Ablation of Cav1 DifferentiallyAffects Melanoma Tumor Growth andMetastasis in Mice: Role of Cav1 in ShhHeterotypic Signaling andTransendothelial MigrationFranco Capozza, Casey Trimmer,Remedios Castello-Cros, Sanjay Katiyar,Diana Whitaker-Menezes, Antonia Follenzi,Marco Crosariol, Gemma Llaverias,Federica Sotgia, Richard G. Pestell, andMichael P. Lisanti
Pr�ecis: Reinforcing the need to study cancer in anorganismal context to gain deeper understanding,a core scaffolding protein in lipid rafts is found toregulate the growth of primary tumors andmetastases quite differently.
2275 The SUMO E3-ligase PIAS1 Regulatesthe Tumor Suppressor PML and ItsOncogenic Counterpart PML-RARAAndrea Rabellino, Brandon Carter,Georgia Konstantinidou, Shwu-Yuan Wu,Alessandro Rimessi, Lauren A. Byers,John V. Heymach, Luc Girard,Cheng-Ming Chiang, Julie Teruya-Feldstein, andPier Paolo Scaglioni
Pr�ecis: Findings offer mechanistic insights intohow the sumoylation machinery modifiesoncogenic signals regulated by the tumorsuppressor PML, and also the therapeutic responseto leukemias involving PML mutations.
2285 Hypoxia-Inducible Factor-2aActivation Promotes ColorectalCancer Progression by DysregulatingIron HomeostasisXiang Xue, Matthew Taylor, Erik Anderson,Cathy Hao, Aijuan Qu, Joel K. Greenson,Ellen M. Zimmermann, Frank J. Gonzalez, andYatrik M. Shah
Pr�ecis: This study points to an intestinal irontransporter as a tractable candidate target forcolon cancer therapy.
2294 Defining NOTCH3 Target Genes inOvarian CancerXu Chen, Michelle M. Thiaville, Li Chen,Alexander Stoeck, Jianhua Xuan, Min Gao,Ie-Ming Shih, and Tian-Li Wang
Pr�ecis: Target genes regulated by Notch3 are ofinterest given emerging evidence of a role for thisreceptor in programming cancer stem-like cellbehavior in lung and ovarian cancers.
PREVENTION AND EPIDEMIOLOGY
2304 Intragenic ATM Methylation inPeripheral Blood DNA as a Biomarkerof Breast Cancer RiskKevin Brennan, Montserrat Garcia-Closas,Nick Orr, Olivia Fletcher, Michael Jones,Alan Ashworth, Anthony Swerdlow, HeatherThorne on behalf of KConFab Investigators,Elio Riboli, Paolo Vineis, Miren Dorronsoro,Francoise Clavel-Chapelon, Salvatore Panico,N. Charlotte Onland-Moret,Dimitrios Trichopoulos, Rudolf Kaaks,Kay-Tee Khaw, Robert Brown, andJames M. Flanagan
Pr�ecis: As cancer risk studies move from genometo epigenome associations, the use of DNA isolatedfrom peripheral blood cells offers an easilyaccessible sample type for epigenome-wideassociation studies.
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2314 Effects of a Caloric RestrictionWeight Loss Diet and Exercise onInflammatory Biomarkers inOverweight/Obese PostmenopausalWomen: A Randomized ControlledTrialIkuyo Imayama, Cornelia M. Ulrich,Catherine M. Alfano, Chiachi Wang, Liren Xiao,Mark H. Wener, Kristin L. Campbell,Catherine Duggan, Karen E. Foster-Schubert,Angela Kong, Caitlin E. Mason,Ching-Yun Wang, George L. Blackburn,Carolyn E. Bain, Henry J. Thompson, andAnne McTiernan
Pr�ecis: Findings suggest that weight loss with orwithout exercise may reduce risk of breast cancer,possibly due to a reduction in systemicinflammation that may support tumordevelopment or progression.
THERAPEUTICS, TARGETS, ANDCHEMICAL BIOLOGY
2327 Immune Response Is an ImportantAspect of the Antitumor EffectProduced by a CD40L-EncodingOncolytic AdenovirusIulia Diaconu, Vincenzo Cerullo,Mari L.M. Hirvinen, Sophie Escutenaire,Matteo Ugolini, Saila K. Pesonen,Simona Bramante, Suvi Parviainen,Anna Kanerva, Angelica S.I. Loskog,Aristides G. Eliopoulos, Sari Pesonen, andAkseli Hemminki
Pr�ecis: Findings detail the development of a newgeneration of oncolytic adenovirus that is armedwith CD40L, which results in the induction of aTH1-type immune response that causesaccumulation of cytotoxic T cells at the tumor siteand increased antitumor efficacy.
2339 Novel MT1-MMP Small-MoleculeInhibitors Based on Insights intoHemopexin Domain Function inTumor GrowthAlbert G. Remacle, Vladislav S. Golubkov,Sergey A. Shiryaev, Russell Dahl,John L. Stebbins, Andrei V. Chernov,Anton V. Cheltsov, Maurizio Pellecchia, andAlex Y. Strongin
Pr�ecis: Findings reveal that targeting a regulatorydomain of increasing pharmacologic interest inmatrix metalloproteases and other proteins canexert potent antitumor properties.
2350 Impact of Intertumoral Heterogeneityon Predicting Chemotherapy Responseof BRCA1-Deficient Mammary TumorsSven Rottenberg, Marieke A. Vollebergh,Bas de Hoon, Jorma de Ronde,Philip C. Schouten, Ariena Kersbergen,Serge A.L. Zander, Marina Pajic,Janneke E. Jaspers, Martijn Jonkers,Martin Lod�en, Wendy Sol, Eline van der Burg,Jelle Wesseling, Jean-Pierre Gillet,Michael M. Gottesman, Joost Gribnau,Lodewyk Wessels, Sabine C. Linn, Jos Jonkers,and Piet Borst
Pr�ecis: Studies of BRCA1-deficient mammarycancers suggest that tumor heterogeneity makes itdifficult to define gene expression signatures thatcould predict chemotherapy responses.
2362 Translation Initiation Factor eIF4EIs a Target for TumorCell RadiosensitizationThomas J. Hayman, Eli S. Williams,Muhammad Jamal, Uma T. Shankavaram,Kevin Camphausen, and Philip J. Tofilon
Pr�ecis: Findings suggest that an existing agentthat targets a critical component of the translationmachinery might be repositioned as a generalneoadjuvant strategy to heighten radiotherapeuticresponses in cancer, with the potential to exert abroad impact in radiation oncology.
2373 Expression of the p53 Target CDIPCorrelates with Sensitivity toTNFa-Induced Apoptosis inCancer CellsLauren Brown-Endres, David Schoenfeld,Fang Tian, Hyung-Gu Kim, Takushi Namba,C�esar Muñoz-Fontela, Anna Mandinova,Stuart A. Aaronson, and Sam W. Lee
Pr�ecis: This study suggests that the product of ap53 target gene may serve as a predictivebiomarker for TNF-based cancer therapeutics.
2383 S-Glutathionylated Serine ProteinaseInhibitors as Plasma Biomarkersin Assessing Response toRedox-Modulating DrugsChristina L. Grek, Danyelle M. Townsend,Joachim D. Uys, Yefim Manevich,Woodrow J. Coker III, Christopher J. Pazoles,and Kenneth D. Tew
Pr�ecis: Novel blood-based biomarkers will assistin pharmacogenetic design of protocols that testnew drugs.
vi Cancer Research
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2394 Dithiolethiones Inhibit NF-kB Activityvia Covalent Modification in HumanEstrogen Receptor–Negative BreastCancerChristopher H. Switzer, Robert Y.-S. Cheng,Lisa A. Ridnour, Margaret C. Murray,Valerio Tazzari, Anna Sparatore,Piero Del Soldato, Harry B. Hines,Sharon A. Glynn, Stefan Ambs, andDavid A. Wink
Pr�ecis: A novel chemical mechanism to inhibitNF-kB activation in aggressive estrogen receptor–negative breast cancers may blunt their invasivecapabilities.
TUMOR AND STEM CELL BIOLOGY
2405 p120RasGAP-Mediated Activation ofc-Src Is Critical for Oncogenic Ras toInduce Tumor InvasionPo-Chao Chan and Hong-Chen Chen
Pr�ecis: The requirement for c-Src in tumorinvasion evoked by oncogenic Ras hasimplications for the development of therapies totarget the Ras pathway, long a goal of the field.
2416 Estrogen Receptor Alpha MediatesProgestin-Induced Mammary TumorGrowth by Interacting withProgesterone Receptors at the CyclinD1/MYC PromotersSebasti�an Giulianelli, Jos�e P. Vaqu�e,Rocío Soldati, Victoria Wargon, Silvia I. Vanzulli,Rub�en Martins, Eduardo Zeitlin,Alfredo A. Molinolo, Luisa A. Helguero,Caroline A. Lamb, J. Silvio Gutkind, andClaudia Lanari
Pr�ecis: Antiestrogens block progesterone-inducedtumor growth because they disrupt estrogenreceptor–progesterone receptor interactions thatare essential for target gene transcription.
2428 Proteomic Portrait of Human BreastCancer Progression Identifies NovelPrognostic MarkersTamar Geiger, Stephen F. Madden,William M. Gallagher, Juergen Cox, andMatthias Mann
Pr�ecis: In performing the deepest proteomicanalysis of breast cancer progression to date, thisstudy identifies novel prognostic markers foroverall survival that function in metabolic andsecretory processes.
2440 Suppression of the Epithelial–Mesenchymal Transition byGrainyhead-like-2Benjamin Cieply, Philip Riley IV, Phillip M. Pifer,Joseph Widmeyer, Joseph B. Addison,Alexey V. Ivanov, James Denvir, andSteven M. Frisch
Pr�ecis: A gene involved in wound healing andneural tube closure is found to be a suppressor ofoncogenic epithelial–mesenchymal transition, apivotal process in cancer cells that is tightlyassociated with the capacity for metastaticprogression.
ABOUT THE COVER
Galectin-3 binding protein, a glycoprotein produced by neuroblastoma cells,upregulates the expression of interleukin-6 in bone marrow mesenchymalcells by interacting with galectin-3. Using immunofluorescence, it wasfound that the galectin-3 binding protein colocalizes with galectin-3 at thesurface and in the cytosol of mesenchymal cells. This interaction generates aRas/MEK/ERK-dependent signal that transcriptionally upregulates theproduction of interleukin-6 in the bone marrow microenvironment.Activation of this pathway contributes to neuroblastoma bone metastasis.For details, see article by Silverman and colleagues on page 2228 of this issue.
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2012;72:2157-2453. Cancer Res 72 (9)
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