title: Lung epithelial cells induce both phenotype alteration and senescence in breast cancer cells.
abstract: OBJECTIVE
  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 senescence markers/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.
authors: Department of Pathology, University of Pittsburgh, and Pittsburgh VA Health System, Pittsburgh, Pennsylvania, United States of America.
authors: Masashi
authors: M
authors: Furukawa
authors: Department of Pathology, University of Pittsburgh, and Pittsburgh VA Health System, Pittsburgh, Pennsylvania, United States of America.
authors: Sarah
authors: S
authors: Wheeler
authors: Department of Pathology, University of Pittsburgh, and Pittsburgh VA Health System, Pittsburgh, Pennsylvania, United States of America.
authors: Amanda M
authors: AM
authors: Clark
authors: Department of Pathology, University of Pittsburgh, and Pittsburgh VA Health System, Pittsburgh, Pennsylvania, United States of America.
authors: Alan
authors: A
authors: Wells
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D016922:Cellular Senescence; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008168:Lung / Q000473:pathology*; D010641:Phenotype
chemical_list: D015820:Cadherins; D019394:Ki-67 Antigen
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