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  • Title: Altered tumor angiogenesis and metastasis of B16 melanoma in transgenic mice overexpressing tissue inhibitor of metalloproteinases-1.
    Author: de Lorenzo MS, Ripoll GV, Yoshiji H, Yamazaki M, Thorgeirsson UP, Alonso DF, Gomez DE.
    Journal: In Vivo; 2003; 17(1):45-50. PubMed ID: 12655789.
    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.
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