MMTV-NeuT/ATTAC mice: a new model for studying the stromal tumor microenvironment

Oncotarget
Hongyan YuanRobert I Glazer

Abstract

One of the central challenges in cancer prevention is the identification of factors in the tumor microenvironment (TME) that increase susceptibility to tumorigenesis. One such factor is stromal fibrosis, a histopathologic negative prognostic criterion for invasive breast cancer. Since the stromal composition of the breast is largely adipose and fibroblast tissue, it is important to understand how alterations in these tissues affect cancer progression. To address this question, a novel transgenic animal model was developed by crossing MMTV-NeuT mice containing a constitutively active ErbB2 gene into the FAT-ATTAC (fat apoptosis through targeted activation of caspase 8) background, which expresses an inducible caspase 8 fusion protein targeted to mammary adipose tissue. Upon caspase 8 activation, lipoatrophy of the mammary gland results in stromal fibrosis and acceleration of mammary tumor development with an increase in tumor multiplicity. Fibrosis was accompanied by an increase in collagen deposition, α-smooth muscle actin and CD31 expression in the tumor stroma as well as an increase in PD-L1-positive tumor cells, and infiltration by regulatory T cells, myeloid-derived suppressor cells and tumor-associated macrophages. Gene ex...Continue Reading

References

Jan 1, 1993·Epidemiologic Reviews·A M Oza, N F Boyd
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Jan 23, 2002·Oncogene·Scott AcklerRobert I Glazer
Nov 19, 2004·Nature·Neil A BhowmickHarold L Moses
Mar 1, 2005·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Tong LiNorman Boyd
Mar 31, 2006·Nature Reviews. Cancer·Raghu Kalluri, Michael Zeisberg
Jun 27, 2006·Breast Cancer Research : BCR·Jasmeet K GillLaurence N Kolonel
Apr 29, 2008·Nature Medicine·Greg FinakMorag Park
May 29, 2008·Molecular Cancer Research : MCR·Vassiliki GioniDimitris Kletsas
Dec 5, 2008·Trends in Genetics : TIG·Kornelia PolyakIan G Campbell
Dec 17, 2008·Nature Reviews. Drug Discovery·Richard Horuk
Dec 31, 2008·Molecular and Cellular Biology·Tayeba KhanPhilipp E Scherer
Feb 4, 2009·Breast Cancer Research : BCR·Xiao-Jun MaDennis C Sgroi
Mar 10, 2010·Experimental Cell Research·Kristian Pietras, Arne Ostman
Mar 23, 2010·Cell·Sergei I GrivennikovMichael Karin
Jul 6, 2010·Developmental Biology·Shira Landskroner-EigerPhilipp E Scherer
Jul 10, 2010·Journal of the National Cancer Institute·Norman F BoydSalomon Minkin
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Geeta UpadhyayRobert I Glazer
Jun 18, 2011·Endocrine-related Cancer·Jiyoung Park, Philipp E Scherer
Dec 24, 2011·Nature·Ira MellmanGlenn Dranoff
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Mar 24, 2012·Cancer Cell·Douglas Hanahan, Lisa M Coussens
Jul 10, 2012·Cell·Swarnali AcharyyaJoan Massagué
Aug 28, 2012·The Journal of Clinical Investigation·Thomas JamiesonOwen J Sansom
Sep 1, 2012·Frontiers in Immunology·Anika Stadtmann, Alexander Zarbock
Nov 21, 2013·Pathology, Research and Practice·Makito MiyakeCharles J Rosser
Jan 11, 2014·Seminars in Cancer Biology·James Harper, Richard C A Sainson
May 23, 2014·Science Translational Medicine·Steven L HighfillCrystal L Mackall

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
chip
Gene
PCR

Software Mentioned

Ariadne Pathway Studio
Prism GraphPad
Affymetrix GeneChip ® Operating

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.