Modelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias
Abstract
When trying to explore the biology and etiology of human cancers, clinically relevant human culture models are essential. Current breast tumour models, such as those from oncogenically transformed primary breast cells, produce predominantly basal-like properties, whereas the more common phenotype expressed by the vast majority of breast tumours are luminal. Reasons for this puzzling, yet important phenomenon, are not understood. We show here that luminal epithelial cells are significantly more resistant to viral transduction than their myoepithelial counterparts. Here, we suggest that this is a significant barrier to generating luminal cell lines and experimental tumours in vivo and to accurate interpretation of results. We show that the resistance is due to lower affinity of luminal cells for virus attachment, which can be overcome by pretreating cells—or virus—with neuraminidase. We present an analytical method for quantifying transductional differences between cell types and an optimized protocol for transducing unsorted primary human breast cells in context.
- Authors:
-
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1256019
- Grant/Contract Number:
- AC02-05CH1123; U01CA143233; U54CA112970; R01CA140663; R37CA064786
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature Communications
- Additional Journal Information:
- Journal Volume: 6; Journal ID: ISSN 2041-1723
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Cancer; breast cancer
Citation Formats
Hines, William C., Yaswen, Paul, and Bissell, Mina J. Modelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias. United States: N. p., 2015.
Web. doi:10.1038/ncomms7927.
Hines, William C., Yaswen, Paul, & Bissell, Mina J. Modelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias. United States. https://doi.org/10.1038/ncomms7927
Hines, William C., Yaswen, Paul, and Bissell, Mina J. Tue .
"Modelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias". United States. https://doi.org/10.1038/ncomms7927. https://www.osti.gov/servlets/purl/1256019.
@article{osti_1256019,
title = {Modelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias},
author = {Hines, William C. and Yaswen, Paul and Bissell, Mina J.},
abstractNote = {When trying to explore the biology and etiology of human cancers, clinically relevant human culture models are essential. Current breast tumour models, such as those from oncogenically transformed primary breast cells, produce predominantly basal-like properties, whereas the more common phenotype expressed by the vast majority of breast tumours are luminal. Reasons for this puzzling, yet important phenomenon, are not understood. We show here that luminal epithelial cells are significantly more resistant to viral transduction than their myoepithelial counterparts. Here, we suggest that this is a significant barrier to generating luminal cell lines and experimental tumours in vivo and to accurate interpretation of results. We show that the resistance is due to lower affinity of luminal cells for virus attachment, which can be overcome by pretreating cells—or virus—with neuraminidase. We present an analytical method for quantifying transductional differences between cell types and an optimized protocol for transducing unsorted primary human breast cells in context.},
doi = {10.1038/ncomms7927},
journal = {Nature Communications},
number = ,
volume = 6,
place = {United States},
year = {Tue Apr 21 00:00:00 EDT 2015},
month = {Tue Apr 21 00:00:00 EDT 2015}
}
Web of Science
Works referenced in this record:
Choosing a Mouse Model: Experimental Biology in Context--The Utility and Limitations of Mouse Models of Breast Cancer
journal, June 2011
- Borowsky, A. D.
- Cold Spring Harbor Perspectives in Biology, Vol. 3, Issue 9
Choosing a Mouse Model: Experimental Biology in Context--The Utility and Limitations of Mouse Models of Breast Cancer
journal, June 2011
- Borowsky, A. D.
- Cold Spring Harbor Perspectives in Biology, Vol. 3, Issue 9
Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice
journal, April 2009
- Wu, Min; Jung, Lina; Cooper, Adrian B.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 17
Dissecting genetic requirements of human breast tumorigenesis in a tissue transgenic model of human breast cancer in mice
journal, April 2009
- Wu, Min; Jung, Lina; Cooper, Adrian B.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 17
Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
journal, January 2001
- Elenbaas, B.
- Genes & Development, Vol. 15, Issue 1
Optimized large-scale production of high titer lentivirus vector pseudotypes
journal, December 2004
- Sena-Esteves, Miguel; Tebbets, Jessica C.; Steffens, Sabine
- Journal of Virological Methods, Vol. 122, Issue 2
Large-Scale Production of Pseudotyped Lentiviral Vectors Using Baculovirus GP64
journal, January 2003
- Kumar, Mukesh; Bradow, Brian P.; Zimmerberg, Joshua
- Human Gene Therapy, Vol. 14, Issue 1
Intrinsic Breast Tumor Subtypes, Race, and Long-Term Survival in the Carolina Breast Cancer Study
journal, December 2010
- O'Brien, K. M.; Cole, S. R.; Tse, C. -K.
- Clinical Cancer Research, Vol. 16, Issue 24
Lentiviral Transduction of Mammary Stem Cells for Analysis of Gene Function during Development and Cancer
journal, January 2008
- Welm, Bryan E.; Dijkgraaf, Gerrit J. P.; Bledau, Anita S.
- Cell Stem Cell, Vol. 2, Issue 1
Clinical and Biological Implications of the Tumor Microenvironment
journal, February 2012
- Tarin, David
- Cancer Microenvironment, Vol. 5, Issue 2
The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression
journal, March 2007
- Kenny, Paraic A.; Lee, Genee Y.; Myers, Connie A.
- Molecular Oncology, Vol. 1, Issue 1
A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes
journal, December 2006
- Neve, Richard M.; Chin, Koei; Fridlyand, Jane
- Cancer Cell, Vol. 10, Issue 6
Unraveling the Mechanisms of Endocrine Resistance in Breast Cancer: New Therapeutic Opportunities
journal, April 2007
- Massarweh, S.; Schiff, R.
- Clinical Cancer Research, Vol. 13, Issue 7
Sorting Out the FACS: A Devil in the Details
journal, March 2014
- Hines, William C.; Su, Ying; Kuhn, Irene
- Cell Reports, Vol. 6, Issue 5
Modelling breast cancer: one size does not fit all
journal, September 2007
- Vargo-Gogola, Tracy; Rosen, Jeffrey M.
- Nature Reviews Cancer, Vol. 7, Issue 9
Stem Cells in the Human Breast
journal, May 2010
- Petersen, O. W.; Polyak, K.
- Cold Spring Harbor Perspectives in Biology, Vol. 2, Issue 5
Creation of human tumour cells with defined genetic elements
journal, July 1999
- Hahn, William C.; Counter, Christopher M.; Lundberg, Ante S.
- Nature, Vol. 400, Issue 6743
Analyses of MYC , ERBB2 , and CCND1 Genes in Benign and Malignant Thyroid Follicular Cell Tumors by Real-Time Polymerase Chain Reaction
journal, February 2001
- Bièche, Ivan; Franc, Brigitte; Vidaud, Dominique
- Thyroid, Vol. 11, Issue 2
Sorting Out the FACS: A Devil in the Details
journal, March 2014
- Hines, William C.; Su, Ying; Kuhn, Irene
- Cell Reports, Vol. 6, Issue 5
Large-Scale Production of Pseudotyped Lentiviral Vectors Using Baculovirus GP64
journal, January 2003
- Kumar, Mukesh; Bradow, Brian P.; Zimmerberg, Joshua
- Human Gene Therapy, Vol. 14, Issue 1
Molecular portraits of human breast tumours
journal, August 2000
- Perou, Charles M.; Sørlie, Therese; Eisen, Michael B.
- Nature, Vol. 406, Issue 6797
Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells
journal, February 1999
- Péchoux, Christine; Gudjonsson, Thorarinn; Rønnov-Jessen, Lone
- Developmental Biology, Vol. 206, Issue 1
Defining the cellular precursors to human breast cancer
journal, September 2011
- Keller, P. J.; Arendt, L. M.; Skibinski, A.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 8
ER-to-Golgi transport visualized in living cells
journal, September 1997
- Presley, John F.; Cole, Nelson B.; Schroer, Trina A.
- Nature, Vol. 389, Issue 6646
Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase
journal, May 2003
- Zhao, Jean J.; Gjoerup, Ole V.; Subramanian, Romesh R.
- Cancer Cell, Vol. 3, Issue 5
Efficient immortalization of luminal epithelial cells from human mammary gland by introduction of simian virus 40 large tumor antigen with a recombinant retrovirus.
journal, May 1991
- Bartek, J.; Bartkova, J.; Kyprianou, N.
- Proceedings of the National Academy of Sciences, Vol. 88, Issue 9
The MCF10 Model of Breast Tumor Progression
journal, August 2021
- Puleo, Julieann; Polyak, Kornelia
- Cancer Research, Vol. 81, Issue 16
Putting tumours in context
journal, October 2001
- Bissell, Mina J.; Radisky, Derek
- Nature Reviews Cancer, Vol. 1, Issue 1
Transformation of Different Human Breast Epithelial Cell Types Leads to Distinct Tumor Phenotypes
journal, August 2007
- Ince, Tan A.; Richardson, Andrea L.; Bell, George W.
- Cancer Cell, Vol. 12, Issue 2
Molecular Distinctions between Stasis and Telomere Attrition Senescence Barriers Shown by Long-term Culture of Normal Human Mammary Epithelial Cells
journal, September 2009
- Garbe, J. C.; Bhattacharya, S.; Merchant, B.
- Cancer Research, Vol. 69, Issue 19
MUC1 and Other Sialoglycoconjugates Inhibit Adenovirus-mediated Gene Transfer to Epithelial Cells
journal, October 1997
- Arcasoy, Selim M.; Latoche, Joseph; Gondor, Magdalen
- American Journal of Respiratory Cell and Molecular Biology, Vol. 17, Issue 4
Toward a Better Understanding of Race and Cancer
journal, December 2010
- Brawley, Otis W.
- Clinical Cancer Research, Vol. 16, Issue 24
Inhibition of adhesion of S-fimbriated Escherichia coli to buccal epithelial cells by human milk fat globule membrane components: a novel aspect of the protective function of mucins in the nonimmunoglobulin fraction.
journal, January 1992
- Schroten, H.; Hanisch, F. G.; Plogmann, R.
- Infection and Immunity, Vol. 60, Issue 7
Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract.
journal, September 1984
- Hammond, S. L.; Ham, R. G.; Stampfer, M. R.
- Proceedings of the National Academy of Sciences, Vol. 81, Issue 17
High-efficiency gene transfer into CD34+ cells with a human immunodeficiency virus type 1-based retroviral vector pseudotyped with vesicular stomatitis virus envelope glycoprotein G.
journal, January 1996
- Akkina, R. K.; Walton, R. M.; Chen, M. L.
- Journal of virology, Vol. 70, Issue 4
Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression
journal, March 2011
- Bissell, Mina J.; Hines, William C.
- Nature Medicine, Vol. 17, Issue 3
Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression
journal, March 2011
- Bissell, Mina J.; Hines, William C.
- Nature Medicine, Vol. 17, Issue 3
Transformation of Different Human Breast Epithelial Cell Types Leads to Distinct Tumor Phenotypes
journal, August 2007
- Ince, Tan A.; Richardson, Andrea L.; Bell, George W.
- Cancer Cell, Vol. 12, Issue 2
Putting tumours in context
journal, October 2001
- Bissell, Mina J.; Radisky, Derek
- Nature Reviews Cancer, Vol. 1, Issue 1
Mammary epithelial cell transformation: insights from cell culture and mouse models
journal, June 2005
- Dimri, Goberdhan; Band, Hamid; Band, Vimla
- Breast Cancer Research, Vol. 7, Issue 4
Phosphatidylserine Is Not the Cell Surface Receptor for Vesicular Stomatitis Virus
journal, September 2004
- Coil, D. A.; Miller, A. D.
- Journal of Virology, Vol. 78, Issue 20
Choosing the right cell line for breast cancer research
journal, August 2011
- Holliday, Deborah L.; Speirs, Valerie
- Breast Cancer Research, Vol. 13, Issue 4
Defining the cellular precursors to human breast cancer
journal, September 2011
- Keller, P. J.; Arendt, L. M.; Skibinski, A.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 8
MUC1 and Other Sialoglycoconjugates Inhibit Adenovirus-mediated Gene Transfer to Epithelial Cells
journal, October 1997
- Arcasoy, Selim M.; Latoche, Joseph; Gondor, Magdalen
- American Journal of Respiratory Cell and Molecular Biology, Vol. 17, Issue 4
Analyses of MYC , ERBB2 , and CCND1 Genes in Benign and Malignant Thyroid Follicular Cell Tumors by Real-Time Polymerase Chain Reaction
journal, February 2001
- Bièche, Ivan; Franc, Brigitte; Vidaud, Dominique
- Thyroid, Vol. 11, Issue 2
Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery
journal, December 1998
- Zufferey, Romain; Dull, Thomas; Mandel, Ronald J.
- Journal of Virology, Vol. 72, Issue 12
Covalent Modifications of the Ebola Virus Glycoprotein
journal, December 2002
- Jeffers, S. A.; Sanders, D. A.; Sanchez, A.
- Journal of Virology, Vol. 76, Issue 24
Efficient immortalization of luminal epithelial cells from human mammary gland by introduction of simian virus 40 large tumor antigen with a recombinant retrovirus.
journal, May 1991
- Bartek, J.; Bartkova, J.; Kyprianou, N.
- Proceedings of the National Academy of Sciences, Vol. 88, Issue 9
Mammary epithelial cell transformation: insights from cell culture and mouse models
journal, June 2005
- Dimri, Goberdhan; Band, Hamid; Band, Vimla
- Breast Cancer Research, Vol. 7, Issue 4
A new diploid nontumorigenic human breast epithelial cell line isolated and propagated in chemically defined medium
journal, March 1987
- Briand, P.; Petersen, O. W.; Deurs, B.
- In Vitro Cellular & Developmental Biology, Vol. 23, Issue 3
Optimized large-scale production of high titer lentivirus vector pseudotypes
journal, December 2004
- Sena-Esteves, Miguel; Tebbets, Jessica C.; Steffens, Sabine
- Journal of Virological Methods, Vol. 122, Issue 2
Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended serial passage with pituitary extract.
journal, September 1984
- Hammond, S. L.; Ham, R. G.; Stampfer, M. R.
- Proceedings of the National Academy of Sciences, Vol. 81, Issue 17
Lentiviral Transduction of Mammary Stem Cells for Analysis of Gene Function during Development and Cancer
journal, January 2008
- Welm, Bryan E.; Dijkgraaf, Gerrit J. P.; Bledau, Anita S.
- Cell Stem Cell, Vol. 2, Issue 1
Modelling breast cancer: one size does not fit all
journal, September 2007
- Vargo-Gogola, Tracy; Rosen, Jeffrey M.
- Nature Reviews Cancer, Vol. 7, Issue 9
Stem Cells in the Human Breast
journal, May 2010
- Petersen, O. W.; Polyak, K.
- Cold Spring Harbor Perspectives in Biology, Vol. 2, Issue 5
Keratin expression in human mammary epithelial cells cultured from normal and malignant tissue: relation to in vivo phenotypes and influence of medium
journal, November 1989
- Taylor-Papadimitriou, J.; Stampfer, M.; Barter, J.
- Journal of Cell Science, Vol. 94, Issue 3
Inhibition of adhesion of S-fimbriated Escherichia coli to buccal epithelial cells by human milk fat globule membrane components: a novel aspect of the protective function of mucins in the nonimmunoglobulin fraction.
journal, January 1992
- Schroten, H.; Hanisch, F. G.; Plogmann, R.
- Infection and Immunity, Vol. 60, Issue 7
High-efficiency gene transfer into CD34+ cells with a human immunodeficiency virus type 1-based retroviral vector pseudotyped with vesicular stomatitis virus envelope glycoprotein G.
journal, January 1996
- Akkina, R. K.; Walton, R. M.; Chen, M. L.
- Journal of virology, Vol. 70, Issue 4
Works referencing / citing this record:
Context-Dependent Function of Myoepithelial Cells in Breast Morphogenesis and Neoplasia
journal, October 2015
- Ingthorsson, Saevar; Hilmarsdottir, Bylgja; Kricker, Jennifer
- Current Molecular Biology Reports, Vol. 1, Issue 4
Oncogenic HrasG12V expression plus knockdown of Cdkn2a using ecotropic lentiviral vectors induces high-grade endometrial stromal sarcoma
journal, October 2017
- Brandt, Laura P.; Albers, Joachim; Hejhal, Tomas
- PLOS ONE, Vol. 12, Issue 10
Isolation of Mouse and Human Tumor-Associated Macrophages
book, January 2016
- Cassetta, Luca; Noy, Roy; Swierczak, Agnieszka
- Tumor Microenvironment
A 3D in vitro model of the human breast duct: a method to unravel myoepithelial-luminal interactions in the progression of breast cancer
journal, April 2017
- Carter, Edward P.; Gopsill, James A.; Gomm, Jennifer. J.
- Breast Cancer Research, Vol. 19, Issue 1
Transformation of enriched mammary cell populations with polyomavirus middle T antigen influences tumor subtype and metastatic potential
journal, October 2015
- Drobysheva, Daria; Smith, Brittni Alise; McDowell, Maria
- Breast Cancer Research, Vol. 17, Issue 1
Laminin signals initiate the reciprocal loop that informs breast-specific gene expression and homeostasis by activating NO, p53 and microRNAs
journal, March 2018
- Furuta, Saori; Ren, Gang; Mao, Jian-Hua
- eLife, Vol. 7
Laminin signals initiate the reciprocal loop that informs breast-specific gene expression and homeostasis by activating NO, p53 and microRNAs
journal, March 2018
- Furuta, Saori; Ren, Gang; Mao, Jian-Hua
- eLife, Vol. 7
Propagation of oestrogen receptor-positive and oestrogen-responsive normal human breast cells in culture
journal, November 2015
- Fridriksdottir, Agla J.; Kim, Jiyoung; Villadsen, René
- Nature Communications, Vol. 6, Issue 1
Transformation of enriched mammary cell populations with polyomavirus middle T antigen influences tumor subtype and metastatic potential
journal, October 2015
- Drobysheva, Daria; Smith, Brittni Alise; McDowell, Maria
- Breast Cancer Research, Vol. 17, Issue 1