Abstract:
:Heparan sulfate 3-O-sulfotransferase 2 (HS3ST2), an enzyme mediating 3-O-sulfation of heparan sulfate (HS), is silenced by hypermethylation in breast cancer. As HS has an important co-receptor function for numerous signal transduction pathways, the phenotypical changes due to HS3ST2 reexpression were investigated in vitro using high and low invasive breast cancer cell lines. Compared to controls, highly invasive HS3ST2-expressing MDA-MB-231 cells showed enhanced Matrigel invasiveness, transendothelial migration and motility. Affymetrix screening and confirmatory real-time PCR and Western blotting analysis revealed increased expression of several matrix metalloproteinases, cadherin-11, E-cadherin and CEACAM-1, while protease inhibitor and annexin A10 expression were decreased. Low invasive HS3ST2 -expressing MCF-7 cells became even less invasive, with no change in gelatinolytic MMP activity. HS3ST2 expression increased HS-dependent basal and FGF2-specific signaling through the constitutively active p44/42 MAPK pathway in MDA-MB-231 cells. Increased MAPK activation was accompanied by upregulation of ß-catenin in MDA-MB-231, and of the transcription factor Tcf4 in both cell lines. Dysregulation of Tcf4-regulated ion transporters and increased cytosolic acidification were observed in HS3ST2-expressing MDA-MB-231 cells, which is a possible underlying cause of increased chemosensitivity towards doxorubicine and paclitaxel in these cells. This study provides the first in vitro evidence of the involvement of HS3ST2 in breast cancer cell invasion and chemosensitivity.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Vijaya Kumar A,Salem Gassar E,Spillmann D,Stock C,Sen YP,Zhang T,Van Kuppevelt TH,Hülsewig C,Koszlowski EO,Pavao MS,Ibrahim SA,Poeter M,Rescher U,Kiesel L,Koduru S,Yip GW,Götte Mdoi
10.1002/ijc.28921subject
Has Abstractpub_date
2014-12-01 00:00:00pages
2579-92issue
11eissn
0020-7136issn
1097-0215journal_volume
135pub_type
杂志文章abstract::Phenotypic and functional characteristics of tumor-infiltrating lymphocytes (TIL) obtained from human primary and metastatic liver tumors were studied. Lymphocytes isolated from 18 tumors and autologous (A) peripheral blood (6 cases) were phenotyped by 2-color flow cytometry and cloned in a limiting dilution system, w...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910460521
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journal_title:International journal of cancer
pub_type: 杂志文章
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journal_title:International journal of cancer
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更新日期:1997-05-16 00:00:00
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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更新日期:1991-01-02 00:00:00
abstract::The causal role of wood-dust exposure in sinonasal cancer (SNC) has been established in epidemiological studies, but the mechanisms of SNC carcinogenesis are still largely unknown. Increased amounts of COX-2 are found in both premalignant and malignant tissues, and experimental evidence link COX-2 to development of ca...
journal_title:International journal of cancer
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更新日期:2008-05-01 00:00:00
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journal_title:International journal of cancer
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更新日期:2014-11-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章,meta分析,评审
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更新日期:2015-05-15 00:00:00
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更新日期:1986-11-15 00:00:00
abstract::Nuclear factor-κB (NF-κB) is constitutively activated in many cancers, including oral squamous cell carcinoma (OSCC), and is involved in the invasive characteristics of OSCC, such as growth, antiapoptotic activity and protease production. However, the cellular mechanism underlying NF-κB's promotion of bone invasion by...
journal_title:International journal of cancer
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更新日期:2012-09-01 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22380
更新日期:2007-02-15 00:00:00
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journal_title:International journal of cancer
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doi:10.1002/ijc.2910250606
更新日期:1980-06-15 00:00:00
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journal_title:International journal of cancer
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更新日期:2000-06-15 00:00:00
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journal_title:International journal of cancer
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更新日期:1999-05-17 00:00:00
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abstract::The roles of fibroblast growth factor-2 (FGF-2) in the hepatocellular carcinoma (HCC) development are still controversial. In this study, we investigated the expression of FGF-2 in chronic hepatitis (CH) type C patients with or without HCC and the immunoregulation of FGF-2 in NK sensitivity of HCC cells. The FGF-2 exp...
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更新日期:2000-05-15 00:00:00
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journal_title:International journal of cancer
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