Altered tumor angiogenesis and metastasis of B16 melanoma in transgenic mice overexpressing tissue inhibitor of metalloproteinases-1

Mariana S. De Lorenzo, Giselle V. Ripoll, Hitoshi Yoshiji, Masaharu Yamazaki, Unnur P. Thorgeirsson, Daniel F. Alonso, Daniel E. Gomez

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Tissue inhibitor of metalloproteinases-1 (TIMP-1) has emerged as a multifunctional protein that plays contrasting roles during angiogenesis and cancer spread. We have investigated the growth, vascularization and metastasis of B16 melanoma cells in a transgenic mouse model with elevated TIMP-1 levels in the systemic circulation. Transgenic C57BL/6j-CBA mice overexpressing human TIMP-1 in the liver under the control of the mouse albumin promoter/enhancer were employed. An early subcutaneous growth advantage and an increased tumor angiogenic response were observed in transgenic animals with respect to wild-type hybrid mice. On the contrary, there was a dramatic decrease in the lung colonizing ability of B16 melanoma cells in TIMP-1 transgenic mice. No significant effect on metastasis formation was observed in another transgenic mouse model with increased TIMP-1 expression in lungs but low plasma levels, where the transgene was placed under the control of the murine mammary tumor virus promoter. These results support the notion that TIMP-1 displays paradoxical effects on tumor progression and suggest that circulating TIMP-1 is efficient in suppressing lung colonization of melanoma cells.

Original languageEnglish (US)
Pages (from-to)45-50
Number of pages6
JournalIn Vivo
Volume17
Issue number1
StatePublished - 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

Keywords

  • Angiogenesis
  • Metastasis
  • TIMP-1
  • Transgenic animal

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