title: Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies.
abstract: BACKGROUND
  Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm.
  
  
  RESULTS
  By integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathways of previously described carcinoma-derived mesenchymal tumor cells (A17) with that of both carcinomas and other mesenchymal phenotypes, such as mesenchymal stem cells (MSCs), breast stroma, and various types of sarcomas. We identified three mesenchymal/stromal-signatures which A17 cells shares with MSCs and breast stroma. By using a recently developed computational approach with publicly available microarray data, we show that these signatures: 1) significantly relates to basal-like breast cancer subtypes; 2) significantly relates to bone metastasis; 3) are up-regulated after hormonal treatment; 4) predict resistance to neoadjuvant therapies.
  
  
  CONCLUSIONS
  Our results demonstrate that mesenchymalization is an intrinsic property of the most aggressive tumors and it relates to therapy resistance as well as bone metastasis.
authors.affiliation: Genetic Immunization Laboratory, Department of Molecular, Cellular and Animal Biology, University of Camerino, Camerino, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Marchini
authors.forename: Maura
authors.initials: M
authors.lastname: Montani
authors.forename: Georgia
authors.initials: G
authors.lastname: Konstantinidou
authors.forename: Rita
authors.initials: R
authors.lastname: Orrù
authors.forename: Silvia
authors.initials: S
authors.lastname: Mannucci
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ramadori
authors.forename: Federico
authors.initials: F
authors.lastname: Gabrielli
authors.forename: Anna
authors.initials: A
authors.lastname: Baruzzi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Berton
authors.forename: Flavia
authors.initials: F
authors.lastname: Merigo
authors.forename: Stefania
authors.initials: S
authors.lastname: Fin
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bisaro
authors.forename: Andrea
authors.initials: A
authors.lastname: Sbarbati
authors.forename: Massimo
authors.initials: M
authors.lastname: Zerani
authors.forename: Mirco
authors.initials: M
authors.lastname: Galiè
authors.forename: Augusto
authors.initials: A
authors.lastname: Amici
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020360:Neoadjuvant Therapy / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2