Prognostic role of syncytin expression in breast cancer

Larsson, Lars‐Inge; Holck, Susanne; Christensen, Ib Jarle

doi:10.1016/j.humpath.2006.10.018

Cited by 59 publications

(47 citation statements)

References 23 publications

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“…ERVWE1 is one of the proteins that is expressed in cancer cells of multiple origins and mediates fusion of cells in human tumors (Larsson et al 2007;Strick et al 2007;Larsen et al 2009). Interestingly, both ERVWE1 and MV have been proposed as candidates for the local treatment of cancer via induction of cell fusion (Msaouel et al 2009;Lin et al 2010).…”

Section: Fusion Of Cancer Cells Leads To Cellular Senescencementioning

confidence: 99%

Cell fusion induced by ERVWE1 or measles virus causes cellular senescence

et al. 2013

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Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers of cellular senescence. During embryonic development, ERVWE1-mediated cell fusion results in formation of the syncytiotrophoblast, which serves as the maternal/fetal interface at the placenta. Expression of ERVWE1 caused cell fusion in normal and cancer cells, leading to formation of hyperploid syncytia exhibiting features of cellular senescence. Infection by the measles virus, which leads to cell fusion, also induced cellular senescence in normal and cancer cells. The fused cells activated the main molecular pathways of senescence, the p53-and p16-pRbdependent pathways; the senescence-associated secretory phenotype; and immune surveillance-related proteins. Thus, fusion-induced senescence might be needed for proper syncytiotrophoblast function during embryonic development, and reuse of this senescence program later in life protects against pathological expression of endogenous fusogens and fusogenic viral infections.

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Section: Fusion Of Cancer Cells Leads To Cellular Senescencementioning

confidence: 99%

Cell fusion induced by ERVWE1 or measles virus causes cellular senescence

et al. 2013

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“…The subject "cell fusion in cancer" is still controversially debated [10,11,13,14] and till now considerably less is known how the multi-step process of cell fusion [15] between tumour cells and other cells is regulated, which also belongs to the molecules being involved in this process. Most of the identified fusion-mediating molecules, e.g., CD47 [16], CD44 [16], CD200 [17], and syncytin-1 [18-20], are expressed on cell types, such as macrophages, knowing to undergo cell fusion during physiological processes. Recent data indicate that fusion events were increased about 10 to 100-fold in liver, brain and intestine in chronic inflammatory conditions [21-23] suggesting that inflammation might be a strong trigger for cell fusion.…”

Section: Introductionmentioning

confidence: 99%

Hybrid cells derived from breast epithelial cell/breast cancer cell fusion events show a differential RAF-AKT crosstalk

et al. 2012

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BackgroundThe biological phenomenon of cell fusion has been linked to several characteristics of tumour progression, including an enhanced metastatogenic capacity and an enhanced drug resistance of hybrid cells. We demonstrated recently that M13SV1-EGFP-Neo breast epithelial cells exhibiting stem cell characteristics spontaneously fused with MDA-MB-435-Hyg breast cancer cells, thereby giving rise to stable M13MDA435 hybrid cells, which are characterised by a unique gene expression profile and migratory behaviour. Here we investigated the involvement of the PLC-β/γ1, PI3K/AKT and RAS-RAF-ERK signal transduction cascades in the EGF and SDF-1α induced migration of two M13MDA435 hybrid cell clones in comparison to their parental cells.ResultsAnalysis of the migratory behaviour by using the three-dimensional collagen matrix migration assay showed that M13SV1-EGFP-Neo cells as well as M13MDA435 hybrid cells, but not the breast cancer cell line, responded to EGF stimulation with an increased locomotory activity. By contrast, SDF-1α solely stimulated the migration of M13SV1-EGFP-Neo cells, whereas the migratory activity of the other cell lines was blocked. Analysis of signal transduction cascades revealed a putative differential RAF-AKT crosstalk in M13MDA435-1 and -3 hybrid cell clones. The PI3K inhibitor Ly294002 effectively blocked the EGF induced migration of M13MDA435-3 hybrid cells, whereas the EGF induced locomotion of M13MDA435-1 hybrid cells was markedly increased. Analysis of RAF-1 S259 phosphorylation, being a major mediator of the negative regulation of RAF-1 by AKT, showed decreased pRAF-1 S259 levels in LY294002 treated M13MDA435-1 hybrid cells. By contrast, pRAF-1 S259 levels remained unaltered in the other cell lines. Inhibition of PI3K/AKT signalling by Ly294002 relieves the AKT mediated phosphorylation of RAF-1, thereby restoring MAPK signalling.ConclusionsHere we show that hybrid cells could evolve exhibiting a differential active RAF-AKT crosstalk. Because PI3K/AKT signalling has been chosen as a target for anti-cancer therapies our data might point to a possible severe side effect of AKT targeted cancer therapies. Inhibition of PI3K/AKT signalling in RAF-AKT crosstalk positive cancer (hybrid) cells could result in a progression of these cells. Thus, not only the receptor (activation) status, but also the activation of signal transduction molecules should be analysed thoroughly prior to therapy.

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“…Within the past decade, several cell fusion associated molecules have been characterized. Most of them are expressed on cell types knowing to undergo cell fusion during physiological processes, whereby a few of these molecules might also play a role in tumor cell fusion including the macrophage fusion receptor (MFR; also known as SIRPa) and its ligands CD47 [20], CD44 [20], and CD200 [21] as well as CD163 [22,23] and syncytin-1 [24][25][26] (a detailed overview of fusogenic molecules is given in [27]). …”

Section: Introductionmentioning

confidence: 99%

Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells

Dittmar

Schwitalla

Seidel

et al. 2010

Clin Exp Metastasis

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Several data of the past years clearly indicated that the fusion of tumor cells and tumor cells or tumor cells and normal cells can give rise to hybrids cells exhibited novel properties such as an increased malignancy, drug resistance, or resistance to apoptosis. In the present study we characterized hybrid cells derived from spontaneous fusion events between the breast epithelial cell line M13SV1-EGFP-Neo and two breast cancer cell lines: HS578T-Hyg and MDA-MB-435-Hyg. Short-tandemrepeat analysis revealed an overlap of parental alleles in all hybrid cells indicating that hybrid cells originated from real cell fusion events. RealTime-PCR-array gene expression data provided evidence that each hybrid cell clone exhibited a unique gene expression pattern, resulting in a specific resistance of hybrid clones towards chemotherapeutic drugs, such as doxorubicin and paclitaxel, as well as a specific migratory behavior of hybrid clones towards EGF. For instance, M13MDA435-4 hybrids showed a marked resistance towards etoposide, doxorubicin and paclitaxel, whereas hybrid clones M13MDA-435-1 and -2 were only resistant towards etoposide. Likewise, all investigated M13MDA435 hybrids responded to EGF with an increased migratory activity, whereas the migration of parental MDA-MB-435-Hyg cells was blocked by EGF, suggesting that M13MDA435 hybrids may have acquired a new motility pathway. Similar findings have been obtained for M13HS hybrids. We conclude from our data that they further support the hypothesis that cell fusion could give rise to drug resistant and migratory active tumor (hybrid) cells in cancer.

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Prognostic role of syncytin expression in breast cancer

Cited by 59 publications

References 23 publications

Cell fusion induced by ERVWE1 or measles virus causes cellular senescence

Cell fusion induced by ERVWE1 or measles virus causes cellular senescence

Hybrid cells derived from breast epithelial cell/breast cancer cell fusion events show a differential RAF-AKT crosstalk

Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells

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