title: Cancer stem-like cells in adenoid cystic carcinoma of salivary glands: relationship with morphogenesis of histological variants.
abstract: BACKGROUND
  Adenoid cystic carcinoma (AdCC) is a common malignant salivary gland tumor. AdCC is histologically characterized as having cribriform, tubular and solid patterns, and production of excess extracellular matrix (ECM). Cancer stem cells (CSCs) are defined cells within a tumor that possess the capacity to self-renew and to induce the heterogeneous lineages of cancer cells that comprise the tumor.
  
  
  METHODS
  To examine the morphogenetic relationship between CSCs and the growth patterns in AdCC, we employed formalin-fixed and paraffin-embedded 26 cases of AdCC and immunohistochemically clarified the distribution of CSCs using CD133 and CD44 antibodies.
  
  
  RESULTS
  CD133- or CD44-positive cancer stem (CS)-like cells were scattered in the pseudocyst-lining area of cribriform patterns having a Swiss cheese-like appearance. However, based on the further overproduction of ECM, CS-like cells accumulate in thin epithelial cords or trabecular arrangements. These CS-like cell aggregations are considered to form two cell-layered tubular patterns. Moreover, proliferation of outer cells in tubular patterns leads to cribriform patterns or solid patterns in the presence of excess ECM production or a lack of ECM overproduction, respectively. CS-like cells in AdCC were frequently located at the border areas adjacent to ECM, with exception of some cribriform and solid variants.
  
  
  CONCLUSIONS
  It is suggested that CSCs included in CD133- or CD44-positive cells play an important role in morphogenesis of salivary AdCC, especially in transition among the histological growth patterns. ECM is well known as a component of the CSC microenvironment, and ECM may regulate morphogenesis of AdCC through the stimulation of CSCs.
authors.affiliation: Division of Oral Pathology and Bone Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. fujishu@nagasaki-u.ac.jp
authors.forename: Shuichi
authors.initials: S
authors.lastname: Fujita
authors.forename: Tohru
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis; D003528:Carcinoma, Adenoid Cystic / Q000473:pathology*; D002449:Cell Aggregation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D049109:Cell Proliferation; D004848:Epithelium / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009024:Morphogenesis / Q000502:physiology; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010455:Peptides / Q000032:analysis; D018987:Salivary Ducts / Q000473:pathology; D012468:Salivary Gland Neoplasms / Q000473:pathology*; D055153:Stem Cell Niche / Q000502:physiology; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides