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::Brain metastases are the most common intracranial tumors in adults, accounting for more than 50% of all such cases. The approach to and management of brain metastases have evolved significantly in recent years due to several reasons. These include advances in neurosurgical and radiotherapeutic techniques, improved sys...
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
abstract::We previously isolated thymosin beta15 from highly metastatic Dunning rat prostatic carcinoma cells. Immunohistochemical study of human prostate cancer specimens revealed a general correlation between Gleason grade and thymosin beta15 expression, with high-grade (more malignant) tumors showing increased staining compa...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006540824969
更新日期:1998-04-01 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::Basement membrane forms widespread barriers to tumor invasion. It has been shown that tumor-secreted, basement membrane-degrading enzymes, namely metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. In this study, we determined the enzymatic activity, content, and mRNA of both the 72 kDa ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00118181
更新日期:1995-11-01 00:00:00
abstract::Breast cancer dissemination can be monitored in patients by detecting circulating and/or disseminated tumor cells. However, bone marrow disseminated tumor cells (BM DTC) may undergo a dormancy during several years before growing (or not) into clinically detectable metastases. We therefore hypothesized that breast canc...
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
abstract::Within the cancer microenvironment, the growth and proliferation of cancer cells in the primary site as well as in the metastatic site represent a global biological phenomenon. To understand the growth, proliferation and progression of cancer either by local expansion and/or metastasis, it is important to understand t...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-018-9921-y
更新日期:2018-08-01 00:00:00
abstract::The function of tropomyosin receptor kinase (Trk) family including TrkA, TrkB, and TrkC in cancer remains unknown. The role of Trks in oral squamous cell carcinoma (OSCC) was examined. Knockdown of Trks provided inhibition of growth or invasion and decrease of apoptosis in OSCC cells, which expressed Trks at high leve...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9525-x
更新日期:2013-02-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-017-9867-5
更新日期:2018-04-01 00:00:00
abstract::Very few tissues in vivo are resistant to invasion by malignant cells. In this paper, confrontation cultures consisting of chick embryonic notochord fragments and cell aggregates from three malignant neurogenic cell lines showed a resistance of the embryonic organ to malignant invasion by tumor cells. The mechanism of...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01769359
更新日期:1991-07-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 临床试验,杂志文章
doi:10.1023/a:1010991213842
更新日期:2000-01-01 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with increasing incidence. Despite curative surgical resection and advanced chemotherapy, its survival rate remains low. The presence of microvascular invasion and occult metastasis is one of the major causes for this poor outcome. MDM2 Binding...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-015-9706-5
更新日期:2015-04-01 00:00:00
abstract::We have examined the effects of the microenvironment on the frequency and generation of metastatic variant cells in both parental B16F1 melanoma cells and nascent clones. The metastatic abilities of cultured B16F1 cells were tested after a period of growth in the presence or absence of a second cell population separat...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01756386
更新日期:1991-03-01 00:00:00
abstract::Emerging evidence suggests that gap junctional intercellular communication (GJIC) and expression of connexins (Cx) contribute to the metastatic potential of breast cancer cells. To more directly address this, an aggressive bone metastasis breast cancer cell line, MDA-MET (MET), was stably transfected with human Cx43 c...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9140-4
更新日期:2008-01-01 00:00:00
abstract::Development of central nervous system (CNS) metastases in breast cancer (BC) is associated with poor prognosis. The incidence of CNS metastases in metastatic BC is reported to be about 10-16 %, but different subtypes of BC are associated with different risk of developing CNS metastases. We retrospectively analysed the...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-013-9594-5
更新日期:2013-12-01 00:00:00
abstract::To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into ac...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,多中心研究
doi:10.1007/s10585-014-9685-y
更新日期:2015-01-01 00:00:00
abstract::In this study, we investigated the therapeutic effects of adenovirally-mediated transfer of the sequence of NK4, an antagonist for hepatocyte growth factor (HGF), against human pancreatic carcinoma. HGF has been implicated to play an important role in invasion and metastasis of various human cancers through tumor-stro...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1016395316362
更新日期:2002-01-01 00:00:00
abstract::Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play important roles in several biological processes and dysregulated lncRNAs are involved in different kinds of cancer and are associated with carcinogenesis, metastasis, and prognosis of cancer. The role of a new lncRNA LOC100130476 in gastric cardi...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-016-9794-x
更新日期:2016-06-01 00:00:00
abstract::The concurrent administration of Metrazol (60 mg/kg, i.v.) to anaesthetized rats enhances the cerebral penetration of the anticancer agent razoxane. Such an enhancement leads to an increase in the therapeutic efficacy of razoxane against intracerebrally sequestered L1210 leukaemia cells in mice. The combination of Met...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00132306
更新日期:1984-01-01 00:00:00
abstract::Two new compounds, 4-[4-[bis-(2-chloroethyl)-amino-]phenyl]-1- hydroxybutane-1,1-bisphosphonic acid (BAD) and aminotris-(methylenephosphonato)-diamminoplatinum(II) (ADP) that both have cytostatic and osteotropic properties, have shown good therapeutic efficacy against an osteosarcoma which metastasizes and kills by lu...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01810680
更新日期:1990-07-01 00:00:00
abstract::Breast cancer patients with advanced disease exhibit bone metastases, leading to the formation of osteolytic lesions for which the only currently available treatments are palliative. Here, we describe how we refined a mouse model of human breast cancer metastasis into bone, characterized its transcriptome and demonstr...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9099-1
更新日期:2008-01-01 00:00:00
abstract::Two widely used B16 melanoma cell lines of low and high lung colonizing potential (B16-F1 and B16-F10) were compared in their ability to induce platelet aggregation. The results of these experiments showed a reproducible difference in platelet aggregating activity of these two cell lines which directly correlated with...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00058058
更新日期:1987-04-01 00:00:00
abstract::The effects of the cyclooxygenase (COX)-2 inhibitor nimesulide on bombesin-enhanced peritoneal metastasis of azoxymethane (AOM)-induced intestinal adenocarcinomas were investigated in male Wistar rats. From the beginning of the study, the rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body weight) and s.c...
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
abstract::We have investigated the gelatinase profiles and invasiveness of clonal tumour sublines derived from a spontaneously arising mammary tumour in a Balb/cfC3H mouse. The 67NR. 66c14 and 4T1.2 sublines have low, intermediate and high metastatic potential respectively. In Boyden chamber studies, Matrigel invasion was seen ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1011953118186
更新日期:2000-01-01 00:00:00
abstract::We have compared the pattern of surface antigen expression, as detected by monoclonal antibodies (mAbs), in plasma membranes vs shed membrane vesicles of two human breast carcinoma cell lines, MCF-7 and 8701-BC. Antigen expression was detected on cells by immunofluorescence (IF) analysis, whilst, due to their small di...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00133483
更新日期:1995-07-01 00:00:00
abstract::A variant cell line (EL-4ad) which adhered to a tissue culture dish was isolated from highly metastatic EL-4 murine T-lymphoma. The experimental and spontaneous metastatic ability of EL-4ad was lower than that of the EL-4 parent cell line. The cell surface phenotypes of both cell lines were CD2+3+4-8-45+TCR alpha beta...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00058169
更新日期:1992-09-01 00:00:00
abstract::Two variant sublines of the murine 3LL carcinoma with divergent potentials for lymphatic metastasis were used to assess the relationship between tumor cell potential for lymphatic metastasis and its ability to adhere specifically to lymphatic tissue. Using fresh cryostat sections of lymph nodes and spleens, it was fou...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01753685
更新日期:1989-05-01 00:00:00
abstract::RGD-containing substrates were used to study static and hydrodynamic adhesion of murine RAW117 large-cell lymphoma sublines with differential liver-metastatic potentials. Highly liver-metastatic RAW117-H10 cells had higher rates of static adhesion to vitronectin, fibronectin and (GRGDS)4 than poorly metastatic RAW117-...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1018451616309
更新日期:1997-01-01 00:00:00
abstract::NIH3T3 cells transfected with an activated Ha-ras oncogene were treated with L-PHA, the leukoagglutinin from red kidney beans. Cell lines resistant to L-PHA-mediated cytotoxicity were isolated and found to contain reduced levels of L-PHA-binding oligosaccharides. The levels of N-acetylglucosaminyltransferase V, the en...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01784333
更新日期:1994-01-01 00:00:00
abstract::Vascularization of solid tumors is thought to occur by sprouting or intussusceptive angiogenesis, co-option of existing vessels, and vasculogenic mimicry after the onset of tumor hypoxia, when the tumor radius exceeds the oxygen diffusion distance. In contrast, here we show that individual endothelial cells that are i...
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
abstract::Breast cancer has a predilection for metastasis to the bone marrow. The preprotachykinin-I (PPT-I) gene has a central role in the early migration of breast cancer cells into the bone marrow, making this organ a latent repository of the cancer cells. This study investigated whether the invasive and metastatic potential...
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