Tracking cells in epithelial acini by light sheet microscopy reveals proximity effects in breast cancer initiation.

ELife
Ashna AlladinMartin Jechlinger

Abstract

Cancer clone evolution takes place within tissue ecosystem habitats. But, how exactly tumors arise from a few malignant cells within an intact epithelium is a central, yet unanswered question. This is mainly due to the inaccessibility of this process to longitudinal imaging together with a lack of systems that model the progression of a fraction of transformed cells within a tissue. Here, we developed a new methodology based on primary mouse mammary epithelial acini, where oncogenes can be switched on in single cells within an otherwise normal epithelial cell layer. We combine this stochastic breast tumor induction model with inverted light-sheet imaging to study single-cell behavior for up to four days and analyze cell fates utilizing a newly developed image-data analysis workflow. The power of this integrated approach is illustrated by us finding that small local clusters of transformed cells form tumors while isolated transformed cells do not.

References

Sep 1, 1988·The New England Journal of Medicine·B VogelsteinJ L Bos
Dec 5, 2002·Physiological Genomics·Ernesto BockampBernhard Zabel
Dec 3, 2004·Cancer Research·Khawla Al-KurayaGuido Sauter
Sep 1, 2007·Genes & Development·Richard T WilliamsCharles J Sherr
Nov 21, 2007·Bioinformatics·Peter LangfelderSteve Horvath
Mar 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Katrina PodsypaninaHarold E Varmus
Apr 5, 2008·Journal of Cell Science·Minhui Lee, Valeri Vasioukhin
Mar 21, 2009·Nature Protocols·Robert H KutnerJakob Reiser
Jul 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Marie McGovernE Jane Albert Hubbard
Jan 23, 2010·Nature Reviews. Cancer·Brian J ReidThomas L Vaughan
Nov 1, 2011·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Yoichiro Tamori, Wu-Min Deng
Nov 30, 2011·The Journal of Biological Chemistry·Nobuyoshi KosakaTakahiro Ochiya
Nov 30, 2011·Nature Reviews. Clinical Oncology·Carlos L ArteagaLuca Gianni
Jan 20, 2012·Nature·Mel Greaves, Carlo C Maley
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Johanna I PartanenJuha Klefström
Feb 15, 2012·Current Stem Cell Research & Therapy·Daniela F QuailLynne-Marie Postovit
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Nov 17, 2012·Cancer Cell·Luke Martin McCaffreyIan G Macara
Dec 25, 2012·Nature Cell Biology·Bin XueSenthil K Muthuswamy
Apr 30, 2013·Development, Growth & Differentiation·Takaya Abe, Toshihiko Fujimori
Sep 26, 2013·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Ian G Macara, Luke McCaffrey
Feb 5, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Stephan Joel ReshkinRosa Angela Cardone
Mar 13, 2014·Cell Stem Cell·Antonija Kreso, John E Dick
Jul 19, 2014·Science·Madeline A Lancaster, Juergen A Knoblich
Jan 15, 2015·Cancer Discovery·Christine L Chaffer, Robert A Weinberg
Apr 30, 2015·Nature·Jarno DrostHans Clevers
Jul 15, 2015·Nature Reviews. Cancer·Doris P Tabassum, Kornelia Polyak
Jun 18, 2016·Cell·Hans Clevers
Jun 24, 2016·Science Translational Medicine·Johanna F DekkersJeffrey M Beekman
Dec 30, 2016·The Journal of Cell Biology·Marina Simian, Mina J Bissell
Jan 31, 2017·Integrative Cancer Science and Therapeutics·Elizabeth A FryKazushi Inoue
May 16, 2017·The Journal of Clinical Investigation·Kristina M HavasMartin Jechlinger
Apr 25, 2018·Nature Medicine·Mikhail BinnewiesMatthew F Krummel
Jun 9, 2019·Trends in Cancer·Philamer C CalsesAnwesha Dey

❮ Previous
Next ❯

Citations

Aug 21, 2020·Nature Reviews. Molecular Cell Biology·Sally Lowell
Nov 20, 2020·Journal of Mammary Gland Biology and Neoplasia·Jakub SumbalZuzana Koledova
Jun 29, 2021·Developmental Biology·Brian GuyRobert J Johnston
Jun 22, 2021·Frontiers in Cell and Developmental Biology·Max A BetjesSander J Tans
Aug 3, 2021·Cells & Development·Alejandro Torres-SánchezGuillaume Salbreux
Sep 10, 2021·Development·Steffen WolfKatie McDole

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
light sheet microscopy
PCR
RNA
transfection
FACS

Software Mentioned

Fiji
Big Data Processor
CATS
Primer3
CATS Fiji
InVi
Big Tools
LAS AF
Imaris

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.