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Clinical & Experimental Metastasis

, Volume 12, Issue 4, pp 296–304 | Cite as

Expression of 72 kDa type IV collagenase and invasion activity of human glioma cells

  • Tatsuya Abe
  • Teruaki Mori
  • Kimitoshi Kohno
  • Motoharu Sciki
  • Taro Hayakawa
  • Howard G. Welgus
  • Shigeaki Hori
  • Michihiko Kuwano
Article

Abstract

Metalloproteinases, inhibitors of metalloproteinases, plasminogen activators, inhibitors of plasminogen activators and cathepsins are thought to be involved in invasion by tumor cells. Glioblastoma multiforme is highly malignant and extremely refractory to therapy. One reason is because of its highly invasive nature within the nervous system. However, it remains unclear how invasion/dissemination of glioblastoma multiforme proceeds. In this study, we attempted to determine which proteinases were responsible for the invasion activity of human glioma cell linesin vitro. Nine human glioma cell lines (NHG1, NHG2, IN157, IN301, IN500, U251, U343, T98G and CCF-STTG1) derived from patients with glioma were grown in culture and used. We compared the invasion activity of glioma cell lines in a Matrigel invasion assay system, and formulated the activity as invasion index (%). Among the nine cell lines, IN157, IN500 and U343 showed less than 10% invasion activity (low group); NHGI, IN301 and CCF-STTG1 showed 10–25% activity (intermediate group); NHG2, U251 and T98G showed more than 30% activity (high group). Addition of an inhibitor of metalloproteinases, TIMP-1, to the assay system was found to significantly inhibit invasion activity of T98G cellsP<0.01). Northern blot analysis demonstrated expression of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and PA inhibitor-1 (PAI-1) in some of the above cell lines. Cellular levels of PAs and their inhibitor mRNA, however, appeared not to be correlated with invasion activity in most glioma cell lines except for CCF-STTG1. Expression of 72 kDa type IV collagenase (MMP-2) was much lower in IN157, IN500 and U343 than other cell lines, whereas expression of TIMP-1 was much higher in IN500 than in other cell lines. Zymographic activity was found to be comparable to MMP-2 mRNA levels in all cell lines except for CCF-STTG1. Type IV collagenolytic activity was also comparable to invasion activity in nine cell lines. These observations suggest the role of type IV collagenase and its inhibitors in determining capacity for invasion by human gliomas. However, a comprehensive analysis bothin vitro andin vivo is required to confirm the role for this enzyme in glioma cell invasiveness.

Keywords

glioma invasion 72 kDa type IV collagenase TIMP 

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Copyright information

© Rapid Communications of Oxford Ltd 1994

Authors and Affiliations

  • Tatsuya Abe
    • 1
  • Teruaki Mori
    • 1
    • 2
  • Kimitoshi Kohno
    • 1
  • Motoharu Sciki
    • 1
    • 3
  • Taro Hayakawa
    • 1
    • 3
  • Howard G. Welgus
    • 1
    • 4
    • 5
  • Shigeaki Hori
    • 2
  • Michihiko Kuwano
    • 1
  1. 1.Department of BiochemistryKyushu University School of MedicineJapan
  2. 2.Department of NeurosurgeryOita Medical UniversityJapan
  3. 3.Department of Virology, Cancer Research InstituteKanazawa UniversityJapan
  4. 4.Department of BiochemistryAichi-Gakuin University School of DentistryNagoyaJapan
  5. 5.Division of DermatologyJewish Hospital at Washington University Medical CenterSt LouisUSA

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