title: Versican G1 and G3 domains are upregulated and latent transforming growth factor-β binding protein-4 is downregulated in breast cancer stroma.
abstract: BACKGROUND
  Cancers are supported by a distinct type of stroma, and versican is overexpressed in the stroma of malignant tumors, including breast cancer. Versican interacts with hyaluronan and fibrillin-1 at its amino terminus (G1) and carboxyl terminus (G3), respectively. Fibrillin-1 also associates with latent transforming growth factor-β binding protein (LTBP)-1 and -4. The detailed alteration of these molecules in breast cancer tissues is still unclear.
  
  
  METHODS
  In 18 patients, alteration of versican, fibrillin-1 and LTBP-1 and 4 was elucidated in comparison with matched normal tissues, using real-time reverse transcriptase polymerase chain reaction, slot blotting and immunohistochemistry. The relationship between the protein expression and clinicopathological features was also investigated.
  
  
  RESULTS
  In breast cancer tissues, mRNAs for versican V1 and V0 were upregulated, and the extracted protein levels of the versican G1 and G3 domains were increased. Meanwhile, LTBP-4 was decreased, and fibrillin-1 and LTBP-1 remained unchanged. The immunohistochemical observations were consistent with the biochemical findings, and the molecules were localized in the stromal tissue rather than in the cancer cells themselves. The expression of versican G3 and G1 domains was positively related to the Ki67 index of carcinoma cells and tumor size, respectively.
  
  
  CONCLUSIONS
  The stromal alterations of versican and LTBP-4 might influence the carcinogenesis and progression of breast tumor cells and modulate their biological phenotypes.
authors.affiliation: Department of Pathology, Osaka Medical College, 2-7 Takatsuki, Osaka, 569-8686, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kuwabara
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yoneda
authors.forename: Zenzo
authors.initials: Z
authors.lastname: Isogai
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Tanigawa
authors.forename: Yuro
authors.initials: Y
authors.lastname: Shibayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D017434:Protein Structure, Tertiary; D012016:Reference Values; D017154:Stromal Cells / Q000378:metabolism; D015854:Up-Regulation; D053675:Versicans / Q000235:genetics* / Q000378:metabolism
chemical_list: C509032:LTBP1 protein, human; C509040:LTBP4 protein, human; D053779:Latent TGF-beta Binding Proteins; C508322:VCAN protein, human; D053675:Versicans