Abstract:
:We applied reverse phase protein microarrays technology to map signal pathway interactions in a discovery set of 34 soft tissue sarcoma (STS) bone metastases compared to healthy bone. Proteins associated with matrix remodeling (MMP), adhesion (FAK Y576/577, Syndecan-1), and growth/survival (IGF1R Y1135/1136, PI3K, EGFR) were elevated in metastasis compared to normal bone. Linkage between Syndecan-1, FAK Y576/577, Shc Y317, and EGFR, IGF Y1135/1136, PI3K/AKT was a prominent feature of STS bone metastasis. Elevated linkage between RANKL and 4EBP1 T37/46, EGFR, IGF1R Y1135/1136, Src Y41, Shc Y317, PI3Kp110γ was associated with short survival. Finally, we tested the hypothesis that signal pathway proteins augmented in the STS bone metastasis may provide clues to understand the subset of primary STS that metastasize. The most representative molecules identified in the discovery set were validated on an independent series of 82 primary STS by immunohistochemistry applied to a tissue microarray. The goal was to correlate the molecular profile in the primary tumors with a higher likelihood of metastasis. Elevation of activated kinase substrate endpoints IRS1 S612, 4EBP1 T37/46, FAK Y576/577 and loss of Fibronectin, were associated with a higher likelihood of metastases. These data indicate that the linkage between matrix remodeling, adhesion, and growth signaling may drive STS metastasis and can be the basis for prognostic and therapeutic strategies.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Conti A,Espina V,Chiechi A,Magagnoli G,Novello C,Pazzaglia L,Quattrini I,Picci P,Liotta LA,Benassi MSdoi
10.1007/s10585-013-9605-6subject
Has Abstractpub_date
2014-01-01 00:00:00pages
15-24issue
1eissn
0262-0898issn
1573-7276journal_volume
31pub_type
杂志文章abstract::In order to study the usefulness of treatment with vinblastine (VLB) in the prevention of cancer metastasis in squamous cell lung cancer, 50 patients with locoregional disease were randomized to receive either locoregional RT alone (group A) or a weekly intravenous bolus injection of VLB (6 mg/m2) concurrently with an...
journal_title:Clinical & experimental metastasis
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::Intravenous infusions of perfluorochemical emulsions, combined with administration of inspired oxygen or carbogen have been found to improve tumor oxygenation and increase the response of solid tumors in animals to radiotherapy. Fluosol-DA 20 per cent, the only perfluorochemical emulsion currently approved for testing...
journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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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
doi:10.1007/s10585-006-9001-6
更新日期:2005-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-009-9276-5
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
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更新日期:1998-11-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-016-9809-7
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:One of the major clinical problems in breast cancer detection is the relatively high incidence of occult lymph node metastases undetectable by standard procedures. Since the ascertainment of breast cancer stage determines the following treatment, such a "hypo-diagnosis" leads to inadequate therapy, and hence...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9135-1
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:10.1023/a:1006649617918
更新日期:1999-01-01 00:00:00
abstract::The spinal column is the most frequent site of bone metastasis in patients with breast cancer. It is important to understand how the pattern of vertebral lesions may be affected by the introduction of modern cancer therapies. The purpose of this study was to characterize changes in the radiological appearance of spina...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-008-9219-6
更新日期:2009-01-01 00:00:00
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 ce...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-006-9007-0
更新日期:2005-01-01 00:00:00
abstract::MicroRNAs have been identified as key players in the development and progression of osteosarcoma, which is the most common primary malignancy of bone. Sequencing-based miR-omic and quantitative real-time PCR analyses suggested that the expression of miR-193a-3p and miR-193a-5p was decreased by DNA methylation at their...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-016-9783-0
更新日期:2016-04-01 00:00:00
abstract::Prostate cancer metastases form selectively in the bone marrow. Previously we demonstrated motility was important for the formation of primary prostatic epithelial cell colonies in bone marrow stroma (BMS) co-culture. In this study we looked at the influence of motility factors on the colony formation of epithelial ce...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006696002497
更新日期:1999-06-01 00:00:00
abstract::Breast cancer metastasizes to bone with high frequency and incidence. However, studies of breast cancer metastasis to bone have been limited by two factors. First, the number of models that colonize bone are limited. Second, detection of bone metastases is too insensitive or too laborious for routine, large-scale stud...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1024062911144
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/s10585-018-9940-8
更新日期:2018-12-01 00:00:00
abstract::Patients with small cell lung cancer (SCLC) are more likely to have synchronous brain metastasis (SBM) at the time of diagnosis than patients with any other extracranial primary malignancy. We sought to identify which factors predicted an increased risk of SBM in SCLC as well as which factors affected the prognosis of...
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
doi:10.1023/a:1006670918848
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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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
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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
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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
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更新日期:1998-04-01 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
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
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更新日期:2011-06-01 00:00:00