Abstract:
:Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival. We found that Reelin expression was low in primary breast cancer tissue. However, its expression was significantly higher in Her2+ breast cancers metastasizing to the brain. In particular, Reelin was highly expressed in the tumor periphery adjacent to surrounding astrocytes. This augmented Reelin expression was seen in Her2+ metastases, but not in triple negative (TN) primary tumors or in TN breast to brain metastasis cells co-cultured with astrocytes. Furthermore, the elevated expression was sustained in Her2+ cells grown in the presence of the DNA methyltransferase inhibitor 5-azacytidine, indicating epigenetic regulation of Reelin expression. The relative growth and rate of spheroids formation derived from Her2+ primary and BBM cells co-cultured with astrocytes were higher than those of TN primary and BBM cells, and knockdown of both Reelin and Her2 suppressed the astrocyte-induced growth and spheroid forming ability of Her2+ cells. Collectively, our results indicate that within the neural niche, astrocytes epigenetically regulate Reelin expression and its interaction with Her2 leading to increased proliferation and survival fitness.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Jandial R,Choy C,Levy DM,Chen MY,Ansari KIdoi
10.1007/s10585-017-9839-9subject
Has Abstractpub_date
2017-02-01 00:00:00pages
185-196issue
2eissn
0262-0898issn
1573-7276pii
10.1007/s10585-017-9839-9journal_volume
34pub_type
杂志文章abstract::A number of papers have been published on the clinical correlation of the expression of the 67 kDa laminin binding protein (LBP) with the metastatic potential of solid tumors. Both mRNA and protein expression levels have been reported, but both the relationship between them and the molecular nature of the 67 kDa surfa...
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
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
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abstract::Mouse mammary carcinoma cells were exposed in vitro to increasing concentrations of doxorubicin hydrochloride [adriamycin (ADR)] or 5-fluorouracil (5-FU). Uptake of [75Se]selenomethionine (75SeM) in a methionine-deficient medium measured the resulting inhibition of protein synthesis by the tumour cells. This was compa...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01753663
更新日期:1989-07-01 00:00:00
abstract::As a reliable model for osteosarcoma is lacking, three human cell lines (SaOS-2, U2OS and 143B) were evaluated in cell-based assays for proliferation, adhesion, migration, invasion, anchorage-independent growth, angiogenesis, mineralised nodule formation, plasmid transfection and oligonucleotide transfection. Tumor ta...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-006-9046-6
更新日期:2006-01-01 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
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::Smad interacting protein 1 (SIP1) is an epithelial-mesenchymal transition (EMT)-inducible gene that plays a key role in tumor progression in various cancers. This study seeks to clarify the clinical and biological significance of SIP1 expression, especially in intestinal type gastric cancer. We analyzed the mRNA level...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9547-4
更新日期:2013-04-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remain...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-021-10074-2
更新日期:2021-01-24 00:00:00
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::High grade serous ovarian tumors often metastasize transperitoneally, a process that begins when small tumor nodules de-adhere and are released into the fluid of the abdominal cavity where they float freely to reach new sites on the peritoneal wall. Podocalyxin, a small anti-adhesive sialomucin, has been shown to cont...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-011-9446-0
更新日期:2012-03-01 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::Type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP9 are implicated in tumor invasion and metastasis. In patients with nasopharyngeal carcinoma (NPC), poor prognosis due to development of local and distant metastasis has been reported to be predicted by antibody titers against the Z protein which is an AP-1...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006699003525
更新日期:1999-07-01 00:00:00
abstract::We aimed to define the clinicopathologic characteristics of breast cancer (BC) patients with brain metastasis (BM) and to investigate the effect of these parameters on survival. Seventy-nine patients diagnosed with BC and symptomatic BM between 1995 and 2011 were retrospectively evaluated. The relationship between cli...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9528-7
更新日期:2013-02-01 00:00:00
abstract::Radiotherapy induces untargeted effects on normal tissues such as bone marrow. So alteration of microenvironment by ionizing irradiation is supposed to influence dynamic host-cancer ecosystem affecting cancer behavior including metastasis. Herein, the incidence of lung metastasis after high-dose irradiation has been i...
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
abstract::The mechanisms leading to rapid invasive growth of malignant gliomas are poorly understood. Expression of the hyaluronic acid (HA) receptor CD44 and adhesion to HA are involved in invasive properties. Our previous studies have shown that malignant glioma cells are able to adhere to extracellular HA. Here we investigat...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1026425519497
更新日期:1999-02-01 00:00:00
abstract::Lung cancer is the most frequent and one of the most deadly cancer types and is classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Transforming growth factor beta (TGFβ) regulates a wide array of cell functions and plays a major role in lung diseases, including NSCLC. TGFβ signals through t...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-013-9598-1
更新日期:2013-12-01 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::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::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::Lymphangiogenesis plays a crucial role in promoting cancer metastasis to sentinel lymph nodes (LNs) and beyond. Increasing data have shown that simvastatin, a cholesterol-lowering medication for the prevention of cardiovascular diseases, is involved in tumor growth and dissemination, and endothelial functions. This st...
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::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::Cancer cells with the surface marker profile CD44+/CD24- have previously been described to possess cancer stem cell-like properties. This manuscript evaluates those properties in ovarian cancer cell lines. The proportion of CD44+/CD24- cells corresponded to the clinical aggressiveness of each ovarian cancer cell line ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9482-4
更新日期:2012-12-01 00:00:00
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, EGF...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-013-9605-6
更新日期:2014-01-01 00:00:00
abstract::Cancer stem cells drive the metastatic cascade by undergoing epithelial to mesenchymal transition (EMT) and again mesenchymal to epithelial transition (MET). Using multiple breast cancer cell lines including cigarette smoke induced breast cancer cells and tumor derived primary cells from patient sample; we developed a...
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::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::The present study assessed the effects of dietary fat on spontaneous metastasis of Lewis lung carcinoma in mice. Three-week old male C57BL/6 mice were fed the AIN-93G diet or a 45% fat diet (% kcal.) for 7 weeks before they were subcutaneously injected with 2.5 × 10⁵ viable carcinoma cells. The primary tumor was resec...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-010-9347-7
更新日期:2010-12-01 00:00:00
abstract::To elucidate the development of bone metastasis in human neuroblastoma, bone marrow and bone metastases were analysed histologically in a hematogeneous metastasis model of murine neuroblastoma. The bone marrow metastasis occurred initially in the bone marrow sinusoid where tumor cells adhered and extravasated to bone ...
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
abstract::Metastasis remains the major cause of therapeutic failure, poor prognosis and high mortality in breast and prostate cancer patients. Aberrant microenvironments including hypoxia and acidic pH are common features of most solid tumors that have been long associated with enhanced metastasis and poor patient outcomes. Nov...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-013-9590-9
更新日期:2013-10-01 00:00:00
abstract::Single cell progenies (SCPs) inherit biological properties from their isogenetic mother cells. If a single cancer cell can give rise to progenies, which can be passaged sustainably in vitro and produce tumor in xenotransplantation, the cell should be cancer initiating cell. CD133 (Prominin-1, Prom1) is the marker of h...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-010-9341-0
更新日期:2010-10-01 00:00:00
abstract::Pulmonary metastasectomy (PM) is an accepted treatment modality in colorectal cancer (CRC) patients with pulmonary tumor spread. Positive intrathoracic lymph nodes at the time of PM are associated with a poor prognosis and 5-year survival rates of <20 %. Increased lymphangiogenesis in pulmonary metastases might repres...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,多中心研究
doi:10.1007/s10585-015-9763-9
更新日期:2016-02-01 00:00:00