title: Cathepsin K-upregulation in fibroblasts promotes matrigel invasive ability of squamous cell carcinoma cells via tumor-derived IL-1α.
abstract: BACKGROUND
  Cathepsin K (CTSK), a cysteine protease with strong collagenolytic properties, is involved in extracellular matrix turnover. In the previous studies, CTSK expression was detected in peritumoral fibroblasts (Fbs) around squamous cell carcinoma (SCC), but not in those surrounding benign epidermal tumors. However, the mechanism governing CTSK expression in epidermal tumors remains unclear.
  
  
  OBJECTIVE
  To study the regulatory mechanisms of fibroblastic CTSK expression in the SCC-stromal interaction.
  
  
  METHODS
  We examined dynamic interactions of Fbs with tumorigenic SCC cells (A431 and A253) or normal human keratinocytes.
  
  
  RESULTS
  SCC cells and normal keratinocytes did not synthesize CTSK, while Fbs constitutively expressed CTSK. When cocultured, SCC cells upregulated fibroblastic CTSK expression more potently than did normal keratinocytes, which was mainly attributable to SCC-derived IL-1α. Coculturing Fbs with SCC cells significantly augmented the matrigel invasive ability of SCC cells, which was downregulated when cocultured with CTSK knockdown Fbs or in the presence of neutralizing anti-IL-1α antibody.
  
  
  CONCLUSIONS
  The CTSK-upregulated Fbs generated by SCC-derived IL-1α may play a crucial role in the progression and invasion of SCC.
authors.affiliation: Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Lining
authors.initials: L
authors.lastname: Xie
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Moroi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hayashida
authors.forename: Gaku
authors.initials: G
authors.lastname: Tsuji
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Baoen
authors.initials: B
authors.lastname: Shan
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakahara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takahara
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018920:Coculture Techniques; D003094:Collagen; D004338:Drug Combinations; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D004338:Drug Combinations; D053582:Interleukin-1alpha; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D003094:Collagen; D056657:Cathepsin K