SCC-25 (squamous cell carcinoma) mediated collagen degradation

L. J. Windsor, L. D. Alexander, H. O. Trummell, G. J. Harber, J. A. Engler

Research output: Contribution to journalArticlepeer-review


Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which have been implicated in the extracellular matrix (ECM) degradation that occurs during tumor invasion and metastasis. The MMPs are secreted as zymogens that require activation, which can be achieved in vitro by treatment with proteases, organomercurials, detergents, or oxidants. However, our knowledge about the mechanism(s) by which live cells activate these enzymes is somewhat limited. To elucidate how live cells activate the MMPs and degrade the ECM, we have identified a cell line (SCC-25) that when seeded on type I collagen is capable of cleaving it without the addition of an external activating factor. A colony of phorbol ester-stimulated SCC-25 cells seeded on a thin film of rat tail type I collagen fibrils could degrade the collagen beneath them in about 24-48 hours. This collagen degradation was not dependent on the addition of external activating factors such as trypsin or plasmin. This aoility to degrade the collagen beneath the cells could be completely blocked by the MMP inhibitor BB-94. Casein and gelatin zymograms of SCC-25 conditioned media showed protease activity at the molecular weight of fibroblast-type collagenase and of Mr 92,000 gelatinase (92K). Western blot analysis of the SCC-25 conditioned media verified the presence of these two MMPs. The unique ability of collagenase to degrade collagen suggest that it plays a major role in the ability of these cells to degrade the collagen beneath them and that these cells contain the mechanism(s) to active the latent enzyme. This work was supported by USPHS grants P50 DE08228, R01 DE10631,andP50CA-13148.

Original languageEnglish (US)
Pages (from-to)A1131
JournalFASEB Journal
Issue number6
StatePublished - Dec 1 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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