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Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells

Furukawa, M and Wheeler, S and Clark, AM and Wells, A (2015) Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells. PLoS ONE, 10 (1).

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Purpose: The lung is one of the most common sites of breast cancer metastasis. While metastatic seeding is often accompanied by a dormancy-promoting mesenchymal to epithelial reverting transitions (MErT), we aimed to determine whether lung epithelial cells can impart this phenotype on aggressive breast cancer cells. Methods: Co-culture experiments of normal lung epithelial cell lines (SAEC, NHBE or BEAS-2B) and breast cancer cell lines (MCF-7 or MDA-MB-231) were conducted. Flow cytometry analysis, immunofluorescence staining for E-cadherin or Ki-67 and senescence associated beta-galactosidase assays assessed breast cancer cell outgrowth and phenotype. Results: Co-culture of the breast cancer cells with the normal lung cells had different effects on the epithelial and mesenchymal carcinoma cells. The epithelial MCF-7 cells were increased in number but still clustered even if in a slightly more mesenchymal-spindle morphology. On the other hand, the mesenchymal MDA-MB-231 cells survived but did not progressively grow out in co-culture. These aggressive carcinoma cells underwent an epithelial shift as indicated by cuboidal morphology and increased E-cadherin. Disruption of E-cadherin expressed in MDA-MB-231 using shRNA prevented this phenotypic reversion in co-culture. Lung cells limited cancer cell growth kinetics as noted by both (1) some of the cells becoming larger and positive for senescencemarkers/negative for proliferation marker Ki-67, and (2) Ki-67 positive cells significantly decreasing in MDA-MB-231 and MCF-7 cells after co-culture. Conclusions: Our data indicate that normal lung epithelial cells can drive an epithelial phenotype and suppress the growth kinetics of breast cancer cells coincident with changing their phenotypes.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Furukawa, M
Wheeler, Ssam125@pitt.eduSAM125
Clark, AMAMC235@pitt.eduAMC235
Wells, Aahw6@pitt.eduAHW6
ContributionContributors NameEmailPitt UsernameORCID
Date: 30 January 2015
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0118060
Schools and Programs: School of Medicine > Pathology
Refereed: Yes
Other ID: NLM PMC4311980
PubMed Central ID: PMC4311980
PubMed ID: 25635394
Date Deposited: 12 May 2015 19:51
Last Modified: 27 Mar 2021 10:55


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