Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype

García, Stéphane; Dalès, Jean-Philippe; Charafe-Jauffret, Emmanuelle; Carpentier-Meunier, Séverine; Andrac-Meyer, Lucile; Jacquemier, Jocelyne; Andonian, Claudine; Lavaut, Marie‐Noëlle; Allasia, Claude; Bonnier, Pascal; Charpin, Colette

doi:10.1016/j.humpath.2006.11.015

Cited by 139 publications

(116 citation statements)

References 32 publications

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“…Interestingly, a similar pattern was found for MET, in accordance with previous reports (38,45,46). c-Met is also associated with poor clinical outcome and considered as a possible marker for earlier recurrence and shorter survival in breast cancer patients (47)(48)(49). Our results support the idea that the products of these two genes may cooperate within the same subtype of breast cancers: the basal type, which consists mainly of the triple-negative breast cancers (ER, progesterone receptor, and erbB2 negative).…”

Section: Discussionsupporting

confidence: 90%

GD3 Synthase Expression Enhances Proliferation and Tumor Growth of MDA-MB-231 Breast Cancer Cells through c-Met Activation

Cazet

Lefebvre

Adriaenssens

et al. 2010

Molecular Cancer Research

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The disialoganglioside G D3 is overexpressed in ∼50% of invasive ductal breast carcinoma, and the G D3 synthase gene (ST8SIA1) displays higher expression among estrogen receptor-negative breast cancer tumors, associated with a decreased overall survival of breast cancer patients. However, no relationship between ganglioside expression and breast cancer development and aggressiveness has been reported. We have previously shown that overexpression of G D3 synthase induces the accumulation of b-and c-series gangliosides (G D3 , G D2 , and G T3 ) at the cell surface of MDA-MB-231 breast cancer cells together with the acquisition of a proliferative phenotype in the absence of serum. Here, we show that phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways are constitutively activated in G D3 synthaseexpressing cells. Analysis of phosphorylation of tyrosine kinase receptors shows a specific c-Met constitutive activation in G D3 synthase-expressing cells, in the absence of its ligand, hepatocyte growth factor/scatter factor. In addition, inhibition of c-Met or downstream signaling pathways reverses the proliferative phenotype. We also show that G D3 synthase expression enhances tumor growth in severe combined immunodeficient mice. Finally, a higher expression of ST8SIA1 and MET in the basal subtype of human breast tumors are observed. Altogether, our results show that G D3 synthase expression is sufficient to enhance the tumorigenicity of MDA-MB-231 breast cancer cells through a ganglioside-dependent activation of the c-Met receptor.

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Section: Discussionsupporting

confidence: 90%

GD3 Synthase Expression Enhances Proliferation and Tumor Growth of MDA-MB-231 Breast Cancer Cells through c-Met Activation

Cazet

Lefebvre

Adriaenssens

et al. 2010

Molecular Cancer Research

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“…22,31 Briefly, cores were punched from the selected 1,200 paraffin blocks (from 1,200 patients), distributed in 6 new blocks including 2 cores for each tumor (200 cases per block, a total of 2,400 cores) of 0.6 mm diameter. To avoid false positive staining that might result from stromal inflammatory cells that could react with the antibodies tested, the tumor areas selected for the TMA 0.6 mm punch were dense carcinomatous areas with minimal stroma including essential vessels and few fibroblasts.…”

Section: Tma Constructionmentioning

confidence: 99%

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23] The latter subtype lacks tailored therapies such as hormone or anti-c-erb B2 therapies.…”

mentioning

confidence: 99%

“…We have focused on quantitative densitometry of immunoprecipitates on digitized microscopic images to provide accurate numerical data that are compatible with requirements for modern statistical analysis (log rank, logistic regression, unsupervised hierarchical clustering). More precisely, in this study we aimed first to confirm the prognostic value of reported immunocytochemical markers, when evaluated with high-throughput standardized assays using tissue microarrays (TMAs) [12][13][14][15][16][17][18][19][20][21][22][23]31 in a large retrospective series of breast carcinomas (n 5 924); second, to quantify the immunohistochemical precipitates within digitized microscopic TMA images, using an automated computer-assisted device; and third, to correlate the quantified immunohistochemical expression of each marker and of groups of markers with patients' outcome. The overall goal was to identify the best group of markers, in terms of sensitivity and specificity, to predict prognosis within 48 hr on tissue sections that would be suitable in clinical practice for individual patients at the time of diagnosis, simultaneously with pathological reporting.…”

mentioning

confidence: 99%

“…The selected markers included a set of 42 prognostic markers known to be indicators of tumor cell growth, proliferation and scattering and of angiogenesis, in addition to markers of some signaling pathways (see review 22 ).…”

mentioning

confidence: 99%

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A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

Charpin

Secq

Giusiano

et al. 2009

Intl Journal of Cancer

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Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow‐up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c‐Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c‐erb B2), and 15 when ER, PgR and c‐erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost‐effective. Quantitative densitometric measurement of immunoprecipitates by computer‐assisted devices from digitized microscopic images allows standardized high‐throughput “in situ” molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies. © 2008 Wiley‐Liss, Inc.

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RETRACTED: Expression of adrenomedullin in human colorectal tumors and its role in cell growth and invasion in vitro and in xenograft growth in vivo

et al. 2013

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Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time quantitative reverse transcription demonstrated a significant expression of AM mRNA in tumor samples from colorectal cancer (CRC) patients in clinical stage II, III, and IV when compared with normal colorectal tissue. AM, CLR, RAMP2, and RAMP3 proteins were immunohistochemically localized in the carcinomatous epithelial compartment of CRC tissue. Tissue microarray analysis revealed a clear increase of AM, CLR, RAMP2, and RAMP3 staining in lymph node and distant metastasis when compared with primary tumors. The human colon carcinoma cells HT-29 expressed and secreted AM into the culture medium with a significant increase under hypoxia. Treatment of HT-29 cells with synthetic AM stimulated cell proliferation and invasion in vitro. Incubation with anti-AM antibody (αAM), anti-AM receptors antibodies (αAMR), or AM antagonist AM22–52 inhibited significantly basal levels of proliferation of HT-29 cells, suggesting that AM may function as an autocrine growth factor for CRC cells. Treatment with αAM significantly suppressed the growth of HT-29 tumor xenografts in vivo. Histological examination of αAM-treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial cells and pericytes, and increased tumor cell apoptosis. These findings highlight the potential importance of AM and its receptors in the progression of CRC and support the conclusion that αAM treatment inhibits tumor growth by suppression of angiogenesis and tumor growth, suggesting that AM may be a useful therapeutic target.

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Poor prognosis in breast carcinomas correlates with increased expression of targetable CD146 and c-Met and with proteomic basal-like phenotype

Cited by 139 publications

References 32 publications

GD3 Synthase Expression Enhances Proliferation and Tumor Growth of MDA-MB-231 Breast Cancer Cells through c-Met Activation

GD3 Synthase Expression Enhances Proliferation and Tumor Growth of MDA-MB-231 Breast Cancer Cells through c-Met Activation

A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays

RETRACTED: Expression of adrenomedullin in human colorectal tumors and its role in cell growth and invasion in vitro and in xenograft growth in vivo

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