Tissue-type plasminogen activator-induced invasion and metastasis of murine melanomas

Hassan Alizadeh, Ding Ma, Michael Berman, Deborah Bellingham, Sarah A. Comerford, Mary Jane H Gething, Joseph F. Sambrook, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

The role of tissue-type plasminogen activator (tPA) in the 'spontaneous' as well as 'experimental' metastasis of ocular melanomas in mice was evaluated by transfecting the D5.1G4 murine melanoma cell line that possesses low metastatic activity and low tPA activity with a full length cDNA encoding human tPA. For comparison, a highly metastatic melanoma cell line (Queen's) that constitutively expresses high tPA production, was transfected with a cDNA coding for human plasminogen activator inhibitor type 1 (PAI-1). Unlike non-transfected controls, transfected D5.1G4 melanoma cells expressed high levels of tPA and produced extensive pulmonary metastases following intravenous injection. By contrast, PAI-1 transfected Queen's melanoma cells expressed low tPA activity and displayed significantly reduced metastatic potential compared with nontransfected controls. Moreover, PAI-1 transfected Queen's melanoma cells did not metastasize from the eye while nontransfected parental cells produced extensive spontaneous metastases. Expression of tPA activity in transfected and nontransfected cell lines was completely blocked by an anti-tPA antibody. This antibody significantly inhibited the organ localization and frequency of lung metastases of both Queen's and tPA-transfected D5.1G4 melanomas. This study demonstrates that tPA is involved in the metastasis of murine intraocular melanomas.

Original languageEnglish (US)
Pages (from-to)449-458
Number of pages10
JournalCurrent Eye Research
Volume14
Issue number6
DOIs
StatePublished - Jan 1 1995

Keywords

  • Intraocular tumor
  • Melanoma
  • Mouse
  • Tissue-type plasminogen activator (tPA)
  • Tumor metastasis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Tissue-type plasminogen activator-induced invasion and metastasis of murine melanomas'. Together they form a unique fingerprint.

  • Cite this