Abstract:
:Osteopontin (OPN) is a glycosylated, secreted phosphoprotein that functions both as a cell attachment and chemotactic factor. Elevated expression of OPN confers enhanced metastatic ability on transformed cells, suggesting that OPN may contribute to the malignant progression of tumors. Migration of mammary carcinoma cells is stimulated by OPN via interactions with integrins and CD44 cell surface receptors. We hypothesized that OPN modulates specific CD44 isoform expression to facilitate breast cancer cell migration. The 21NT tumorigenic human breast cancer cell line was examined for regulation of CD44 expression at both the mRNA and protein levels in response to an engineered increase in OPN expression under CMV promoter control. Significant up-regulation of CD44s isoform mRNA expression was observed, but no change in CD44v6, v8, v9 or v10 mRNA levels. While there were elevated levels of CD44s, v6 and v9 protein at the cell surface, at the level of total cellular protein only CD44s and v6 were markedly increased. This suggests that OPN can regulate CD44 expression at both transcriptional and post-transcriptional (both amount and localization of protein) levels. To validate the functional consequence of OPN regulation of CD44 expression, we demonstrate that OPN-mediated cell migration was reduced by exposure to a anti-pan CD44 antibody, and to anti-CD44v6 and anti-CD44v9 function-blocking antibodies. Our data provide evidence that in 21NT cells OPN enhances CD44s mRNA expression, increases cell surface expression of CD44 variant forms without a change in mRNA levels, and stimulates cell migration.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Khan SA,Cook AC,Kappil M,Günthert U,Chambers AF,Tuck AB,Denhardt DTdoi
10.1007/s10585-006-9007-0subject
Has Abstractpub_date
2005-01-01 00:00:00pages
663-73issue
8eissn
0262-0898issn
1573-7276journal_volume
22pub_type
杂志文章abstract::About 30-40% of patients with renal cell carcinoma (RCC) will develop metastasis after curative nephrectomy. There is a strong need to identify the early metastasis with conventional and molecular risk factors. The present study aimed to test if analysis of the CA9 gene can provide useful information to predict early ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9064-z
更新日期:2007-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-011-9419-3
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-011-9411-y
更新日期:2011-12-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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更新日期:2015-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-011-9446-0
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,多中心研究
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更新日期:2016-02-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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更新日期:1997-03-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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更新日期:1985-04-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-011-9384-x
更新日期:2011-06-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00058055
更新日期:1993-07-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-008-9203-1
更新日期:2008-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-009-9273-8
更新日期:2009-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-017-9865-7
更新日期:2017-10-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-009-9257-8
更新日期:2009-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-018-9892-z
更新日期:2018-08-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00121912
更新日期:1995-09-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00128962
更新日期:1996-10-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-012-9517-x
更新日期:2012-10-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006567229929
更新日期:1998-10-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1013849123736
更新日期:2002-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1025883129932
更新日期:2003-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00132928
更新日期:1984-07-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9126-2
更新日期:2008-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00117793
更新日期:1990-03-01 00:00:00
abstract::Elevated osteopontin (OPN) transcription often correlates with increased metastatic potential of transformed cells, and in several model systems OPN--whether produced by the tumor cells or by stromal cells - has been shown to enhance metastatic ability. Sequence elements in the OPN promoter have been identified on the...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1023/a:1022550721404
更新日期:2003-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/b:clin.0000037697.76011.1d
更新日期:2004-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1021322201816
更新日期:2002-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/b:clin.0000046140.19131.19
更新日期:2004-01-01 00:00:00