Abstract:
:Blood samples, bone marrow, tumours and metastases where possible were collected from SCID mice bearing orthotopic xenografts of the triple-negative MDA-MB-468 cell line or a transplantable ER-positive patient derived xenograft (ED-03), and assessed using human-specific, tandem-nested RT-qPCR for markers relating to detection of circulating (CTCs) and disseminated tumour cells (DTCs), breast cancer clinicopathology, the 'cancer stem cell' phenotype, metabolism, hypoxia and epithelial-mesenchymal plasticity (EMP). Increased levels of SNAI1, ILK, NOTCH1, CK20, and PGR, and a decrease/loss of EPCAM in CTCs/DTCs were observed relative to the primary xenograft across both models. Decreased CD24 and EGFR was restricted to the MDA-MB-468 model, while increased TFF1 was seen in the ED-03 model. The major metabolic regulator PPARGC1A, and several hypoxia-related markers (HIF1A, APLN and BNIP3) were significantly elevated in both models. Increased expression of mesenchymal markers including SNAI1 was seen across both models, however CDH1 did not decrease concordantly, and several other epithelial markers were increased, suggesting an uncoupling of EMP to produce an EMP hybrid or partial-EMT. Single cell analysis of ED-03 CTCs, although limited, indicated uncoupling of the EMP axis in single hybrid cells, rather than distinct pools of epithelial or mesenchymal-enriched cells, however dynamic heterogeneity between CTCs/DTCs cannot be ruled out. Reduced CD24 expression was observed in the MDA-MB-468 CTCs, consistent with the 'breast cancer stem cell' phenotype, and metastatic deposits in this model mostly resembled the primary xenografts, consistent with the mesenchymal-epithelial transition paradigm.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Tachtsidis A,Le AV,Blick T,Gunasinghe D,De Sousa E,Waltham M,Dobrovic A,Thompson EWdoi
10.1007/s10585-019-09977-ysubject
Has Abstractpub_date
2019-08-01 00:00:00pages
393-409issue
4eissn
0262-0898issn
1573-7276pii
10.1007/s10585-019-09977-yjournal_volume
36pub_type
杂志文章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
pub_type: 杂志文章
doi:10.1007/BF00053472
更新日期:1986-01-01 00:00:00
abstract::The effects of treatment of human lung carcinoma cell line A 549 with recombinant DNA-derived human leukocyte interferons A (rIFN-alpha A) or D (rIFN-alpha D), and human lymphoblastoid interferon (Wellferon) on in vitro cell invasion were investigated in a quantitative invasion assay using human amnion. The A 549 cell...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00117932
更新日期:1986-07-01 00:00:00
abstract::The abilities of tumor cells to extravasate from the blood vessel system and to migrate through the connective tissue are prerequisites in metastasis formation. Both processes are chiefly mediated by integrins, which mediate both cell-cell and cell-matrix interactions. We investigated the role of integrin subunits in ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-005-4335-z
更新日期:2005-01-01 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
abstract::We have examined the role of platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) during the transendothelial migration of melanoma cells using a novel in vitro system. Comparable studies have suggested the involvement of PECAM-1 in leukocyte transendothelial migration. Such studies have been confirmed using i...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1011884807746
更新日期:2000-01-01 00:00:00
abstract::We recently developed a method for the isolation and purification of tumour-derived endothelium. In this study the phenotypic and functional properties of human tumour-derived microvascular endothelial cells (TdMEC) were examined. Endothelium obtained from human adrenal gland specimens (HAMEC) was used as a reference ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006738901839
更新日期:1999-01-01 00:00:00
abstract::The purpose of this study was to determine the subpopulation dynamics of human colon carcinoma (HCC) cells growing at orthotopic (cecum, liver) or ectopic (subcutis, kidney, spleen) sites in nude mice and to correlate any outgrowth of distinct clones with the differential expression of metastasis-related genes. Low me...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1018400826845
更新日期:1997-03-01 00:00:00
abstract:PURPOSE:To evaluate lymphangiogenesis in patients with breast carcinoma, explore the underlying mechanism, and study the relationship between lymphangiogenesis and progression of breast carcinoma. METHODS:Sixty-one cases of breast carcinoma with complete clinical and pathological data were analyzed. Using an anti-podo...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-008-9180-4
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/BF01753676
更新日期:1989-11-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01580402
更新日期:1988-01-01 00:00:00
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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::Activation of nuclear factor-κB (NF-κB) has been implicated in metastasis of pancreatic cancer. We investigated the effects of the novel NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) on the inhibition of liver metastasis of pancreatic cancer in a mouse model of clinical liver metastasis. Nude mice were xenogr...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9544-7
更新日期:2013-04-01 00:00:00
abstract::ECA109 human oesophageal carcinoma cells were injected either subcutaneously or intraperitoneally into BALB/CATc 1-nu/nu mice. After 23 weeks tumours were examined histologically and by scanning electron microscopy. Subcutaneous ECA109 tumours were well-delineated without signs of invasion. By contrast, intra-abdomina...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00132927
更新日期:1984-07-01 00:00:00
abstract::Despite an initial response to antihormonal therapies, the development of resistance will occur in a significant number of breast cancer patients. The mechanisms that underlie acquired resistance are not yet clear. Using a previously established in vitro cell model of tamoxifen resistance in MCF7 cells, shown to displ...
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
abstract::The interaction between circulating tumor cells and blood components, mainly platelets, plays an important role during metastasis. In this study, we prepared liposomes containing the platelet aggregation inhibitor Cilostazol (Cil-L). The objective of this study was to investigate the effect of this Cil-L on platelet a...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-009-9299-y
更新日期:2010-01-01 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::Although the loss of sulfomucins was known as an indicator of carcinogenesis and malignant progression of colonic epithelia, it was not known whether the loss was directly related to the malignant behavior of colon carcinoma cells. We have studied the biological properties of LS174T human colon carcinoma cells before ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006654027742
更新日期:1999-03-01 00:00:00
abstract::Using alternative splicing reporters we have previously observed mesenchymal epithelial transitions in Dunning AT3 rat prostate tumors. We demonstrate here that the Dunning DT and AT3 cells, which express epithelial and mesenchymal markers, respectively, represent an excellent model to study epithelial transitions sin...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-008-9186-y
更新日期:2008-01-01 00:00:00
abstract::p38 belongs to a family of mitogen-activated protein kinases, which transfer extracellular signals into intracellular responses. p38 is also frequently detected in clinical breast cancer specimens, but its role as a prognostic factor is not known. Of the various p38 isoforms, p38alpha has been shown to mediate the in ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-004-3503-x
更新日期:2004-01-01 00:00:00
abstract::Human CD44 standard isoform (hCD44s) cDNA regulated by a high-expressing promoter was transfected into Balb/c 3T3 cells and the tumorigenic and metastatic capacities of the transfectants were investigated in nude mice at the subcutaneous site. One of three transfectants was tumorigenic. hCD44s expression was lost in t...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006568103588
更新日期:1998-01-01 00:00:00
abstract::Metastatic bone disease is an important clinical problem which has proven difficult to study because of a lack of noninvasive investigative modalities. Here we show that dual-energy X-ray absorptiometry (DXA) scanning provides clinically useful information about the status of metastatic bone lesions in cancer patients...
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::We have investigated the role of sialylation on cell-cell adhesion mediated by E-cadherin. Two MCF-7 human breast cancer cell variants were studied: MCF-7/AZ cells showed a spontaneous cell-cell adhesion in the fast and slow aggregation assay. whereas the adhesion deficient MCF-7/6 cell variant failed to form larger a...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006639804430
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:Metastasis to bone from endometrial adenocarcinoma is rare, when metastasises it usually locates in axial skeleton. Metastasis to extremities is extremely rare. Additionally the detection of the bone metastasis as a presenting feature is uncommon. In the present study we report the 10th cases of bone metasta...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9061-2
更新日期:2007-01-01 00:00:00
abstract::Emerging data in myeloma and other cancers indicates that heparan sulfate proteoglycans promote tumor progression by enhancing their growth and metastasis. By acting as key regulators of cell signaling via their interactions with multiple growth and angiogenic factors, heparan sulfates mediate a shift in the microenvi...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-007-9125-3
更新日期:2008-01-01 00:00:00
abstract::Lung cancer often metastasizes to bone in patients with advanced disease. Identification of the factors involved in the interactions between lung cancer cells and bone will improve the prevention and treatment of bone metastases. We identified changes in metastasis-related gene expression of human HARA lung squamous c...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9059-9
更新日期:2007-01-01 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::To study the tumor cell autonomous processes of metastasis, an in vivo tumor metastasis model is required that excludes the involvement of the innate immune system. For this purpose we used the established syngeneic MTLn3 cell - Fischer 344 tumor model. MTLn3 cells are efficiently eradicated by NK cells in vivo. Using...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9075-9
更新日期:2007-01-01 00:00:00
abstract::Considering recent findings that cyclooxygensase-2 (COX-2) is involved in the progression of colorectal carcinoma (CRC), the role of COX-2 in promoting invasion and angiogenesis was investigated by evaluating the relationship of COX-2 expression to various clinicopathological variables, including plasminogen activatin...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1020392309715
更新日期:2002-01-01 00:00:00
abstract::In breast tumors, high levels of leptin have been associated with increased incidence of breast cancer metastasis. Breast cancer metastasis is directly associated with breast cancer cell invasion. However, whether leptin could augment breast cancer cell invasion is not known. Here we showed that leptin increased the i...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-008-9231-x
更新日期:2009-01-01 00:00:00
abstract::The milieu of the liver, and in particular hepatocyte-derived extracellular matrix (hECM), is a critical factor regulating development of liver metastases of colorectal cancer (CRC) cells. The present study has investigated genes altered by hECM in CRC cells and particularly by heparan sulfate chains of hepatocyte pro...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9527-8
更新日期:2013-02-01 00:00:00