title: JAK/STAT pathway interacts with intercellular cell adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) while prostate cancer stem cells form tumor spheroids.
abstract: OBJECTIVE
  JAK/STAT is an evolutionarily conserved pathway and very important for second messenger system. This pathway is important in malignant transformation and accumulated evidence indicates that this pathway is involved in tumorigenesis and progression of several cancers. It was possible to assume that activation of JAK/STAT pathway is associated with increase in the expressions of ICAM/1 and VCAM-1. In this study we hypothesized that when cells were maintained as spheroids or monolayers, the structure of cancer stem cells (CSCs) could show differentiation when compared with non-CSCs.
  
  
  METHODS
  DU-145 human prostate cancer cells were cultured using the Ege University molecular embryology laboratory medium supplemented wıth 10% fetal bovine serum. Clusters of differentiation 133 (CD133)(+high)/CD44(+high) prostate CSCs were isolated from the DU145 cell line by using BD FACSAria. CD133//CD44+ CSCs were cultured until confluent with 3% noble agar. The expression of these proteins in CSCs and non-CSCs was analyzed by immunohistochemistry.
  
  
  RESULTS
  Different expression profiles were observed in the conventional two-dimensional (2D) and three-dimensional (3D) experimental model system when CSCs and non-CSCs were compared. Human prostate CSCs exhibited intense ICAM-1 and VCAM-1 immunoreaction when compared with non-CSCs. These findings were supported by the fact that VCAM-1 on the surface of cancer cells binds to its counterreceptor, the α4β1 integrin (also known as very-late antigen, VLA-4), on metastasis-associated macrophages, triggering VCAM-1-mediated activation of the phosphoinositide 3-kinase growth and survival pathway in cancer cells.
  
  
  CONCLUSIONS
  The results of this study showed that changes in JAK/STAT pathway are related with adhesion molecules and could affect cancer progression.
authors.affiliation: Department of Stem Cell, Institute of Health Sciences, Ege University, Izmir, Turkey.
authors.forename: Fahriye
authors.initials: F
authors.lastname: Duzagac
authors.forename: Sevinc
authors.initials: S
authors.lastname: Inan
authors.forename: Fatma
authors.initials: F
authors.lastname: Ela Simsek
authors.forename: Eda
authors.initials: E
authors.lastname: Acikgoz
authors.forename: Ummu
authors.initials: U
authors.lastname: Guven
authors.forename: Shafiq A
authors.initials: SA
authors.lastname: Khan
authors.forename: Hadi
authors.initials: H
authors.lastname: Rouhrazi
authors.forename: Fatih
authors.initials: F
authors.lastname: Oltulu
authors.forename: Huseyin
authors.initials: H
authors.lastname: Aktug
authors.forename: Ayse
authors.initials: A
authors.lastname: Erol
authors.forename: Gulperi
authors.initials: G
authors.lastname: Oktem
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*; D053612:Janus Kinases / Q000502:physiology*; D008297:Male; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D050791:STAT Transcription Factors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D018874:Spheroids, Cellular / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*
chemical_list: D050791:STAT Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D053612:Janus Kinases