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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2006-2-27
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pubmed:abstractText |
Previously, we showed that bikunin, a Kunitz-type protease inhibitor, inhibits invasion and metastasis in several types of cancer cells possibly through suppression of upregulation of urokinase-type plasminogen activator (uPA) expression. Bikunin corresponds to a light chain of the inter-alpha inhibitor. To explore critical role of endogenous bikunin, we used bikunin knockout (Bik-/-) mice. Here, we show that 1) higher frequency of spontaneous 3LL lung metastasis was observed in Bik-/- mice compared to Bik+/+ mice, suggesting that bikunin deficiency increases the sensitivity of mice to lung metastasis; 2) administration of exogenous bikunin caused a significant reduction of lung metastasis in Bik-/- and Bik+/+ mice; 3) primary and metastatic tumors significantly upregulated uPA and PAI-1 expression in Bik-/- mice relative to Bik+/+ mice at least through phosphorylation of ERK1/2 and 4) exogenous bikunin suppressed phosphorylation of ERK1/2 and upregulation of uPA and PAI-1 expression in 3LL cells in response to G-CSF. These data allow us to conclude that the increased sensitivity of Bik-/- mice to lung metastasis in vivo is due to a lack of circulating proteins of the inter-alpha inhibitor family, especially bikunin.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0020-7136
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pubmed:author |
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pubmed:copyrightInfo |
2005 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2322-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16331631-Animals,
pubmed-meshheading:16331631-Carcinoma, Lewis Lung,
pubmed-meshheading:16331631-Genetic Predisposition to Disease,
pubmed-meshheading:16331631-Lung Neoplasms,
pubmed-meshheading:16331631-Membrane Glycoproteins,
pubmed-meshheading:16331631-Mice,
pubmed-meshheading:16331631-Mice, Inbred C57BL,
pubmed-meshheading:16331631-Mice, Inbred ICR,
pubmed-meshheading:16331631-Mice, Knockout,
pubmed-meshheading:16331631-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:16331631-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:16331631-Phosphorylation,
pubmed-meshheading:16331631-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:16331631-Trypsin Inhibitor, Kunitz Soybean,
pubmed-meshheading:16331631-Up-Regulation,
pubmed-meshheading:16331631-Urokinase-Type Plasminogen Activator
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pubmed:year |
2006
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pubmed:articleTitle |
Enhanced spontaneous metastasis in bikunin-deficient mice.
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pubmed:affiliation |
NetForce Co., Ltd., Nakamura, Nagoya, Aichi, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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