Publication Date:
2015-11-13
Description:
The role of epithelial-to-mesenchymal transition (EMT) in metastasis is a longstanding source of debate, largely owing to an inability to monitor transient and reversible EMT phenotypes in vivo. Here we establish an EMT lineage-tracing system to monitor this process in mice, using a mesenchymal-specific Cre-mediated fluorescent marker switch system in spontaneous breast-to-lung metastasis models. We show that within a predominantly epithelial primary tumour, a small proportion of tumour cells undergo EMT. Notably, lung metastases mainly consist of non-EMT tumour cells that maintain their epithelial phenotype. Inhibiting EMT by overexpressing the microRNA miR-200 does not affect lung metastasis development. However, EMT cells significantly contribute to recurrent lung metastasis formation after chemotherapy. These cells survived cyclophosphamide treatment owing to reduced proliferation, apoptotic tolerance and increased expression of chemoresistance-related genes. Overexpression of miR-200 abrogated this resistance. This study suggests the potential of an EMT-targeting strategy, in conjunction with conventional chemotherapies, for breast cancer treatment.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662610/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4662610/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fischer, Kari R -- Durrans, Anna -- Lee, Sharrell -- Sheng, Jianting -- Li, Fuhai -- Wong, Stephen T C -- Choi, Hyejin -- El Rayes, Tina -- Ryu, Seongho -- Troeger, Juliane -- Schwabe, Robert F -- Vahdat, Linda T -- Altorki, Nasser K -- Mittal, Vivek -- Gao, Dingcheng -- 1 F31 CA186510-01/CA/NCI NIH HHS/ -- F31 CA186510/CA/NCI NIH HHS/ -- R01 CA135417/CA/NCI NIH HHS/ -- U01 CA188388/CA/NCI NIH HHS/ -- U54 CA149196-05/CA/NCI NIH HHS/ -- England -- Nature. 2015 Nov 26;527(7579):472-6. doi: 10.1038/nature15748. Epub 2015 Nov 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA. ; Department of Cell and Developmental Biology, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA. ; Neuberger Berman Lung Cancer Center, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA. ; Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA. ; Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas 77030, USA. ; Methodist Cancer Center, Houston Methodist Hospital, Houston, Texas, 77030 USA. ; Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, 25 Bongjeong-ro Cheonan-Si, Chungcheongnam-do 31151, South Korea. ; Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA. ; Institute of Human Nutrition, Columbia University, New York, New York 10032, USA. ; Department of Medicine, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26560033" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antineoplastic Agents, Alkylating/pharmacology/therapeutic use
;
Apoptosis/drug effects
;
Cell Lineage
;
Cell Proliferation/drug effects
;
Cell Tracking
;
Cyclophosphamide/pharmacology/therapeutic use
;
Disease Models, Animal
;
Disease Progression
;
*Drug Resistance, Neoplasm/drug effects/genetics
;
*Epithelial-Mesenchymal Transition/drug effects/genetics
;
Female
;
Lung Neoplasms/drug therapy/genetics/*pathology/*secondary
;
Male
;
Mammary Neoplasms, Experimental/*drug therapy/genetics/*pathology
;
Mice
;
MicroRNAs/genetics
;
Neoplasm Metastasis/drug therapy/genetics/*pathology
;
Reproducibility of Results
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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