Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Wever, Olivier De; Pauwels, Patrick; Craene, Bram De; Sabbah, Michèle; Emami, Shahin; Redeuilh, Gérard; Gespach, Christian; Bracke, Marc; Berx, Geert

doi:10.1007/s00418-008-0464-1

Cited by 197 publications

(185 citation statements)

References 150 publications

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“…101 Alternatively, mutated stromal cells might be cancer cells that have undergone epithelial-to-mesenchymal transition. 102 It is important that, in the natural situation in vivo, the tumor is not composed solely of cancer cells and tumor-associated host myofibroblasts (Fig. 4).…”

Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 99%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

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616

596

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Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer-associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow-derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor-associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth-promoting factors, through direct cell-cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis.

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Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 99%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

Self Cite

616

596

View full text Add to dashboard Cite

show abstract

“…Epithelial-mesenchymal transition contributes to cancer cell plasticity by increasing cell invasiveness and metastatic potential, and is characterized by loss or relocalization of epithelial markers (eg, E-cadherin and b-catenin) and gain of mesenchymal markers (eg, N-cadherin and smooth muscle actin). 34 Cadherins are known regulators of cell differentiation, and E-cadherin is the prime mediator of cell-cell adhesion among epithelial cells, including the oviductal, endometrial, and cervical epithelia. 35 The ovarian surface epithelium (OSE) is a major target tissue for ovarian carcinoma formation and pre-neoplastic ovarian surface epithelial cells are cohesive, non-migratory, and express E-cadherin.…”

Section: Vegfr2 Rnai Knockdown Increases Eoc Malignancy Sai Adham Et Almentioning

confidence: 99%

Molecular blockade of VEGFR2 in human epithelial ovarian carcinoma cells

Adham

Sher

Coomber

2010

Laboratory Investigation

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Human epithelial ovarian cancer (EOC) is the most lethal neoplasm affecting the female genital tract, and is characterized by overexpression of vascular endothelial growth factor (VEGF) and growth as ascites. Anti-VEGF strategies are currently used in EOC therapy with promising results; however, molecular targeting of specific VEGF receptors on the cancer cells themselves has not been explored to date. We previously showed that activation of a VEGF/VEGFR2 signaling loop in EOC cells supports their survival in suspension, and short-term pharmacological inhibition of this loop increased EOC cell apoptosis in vitro. In this study, we stably knocked down VEGFR2 in OVCAR-3 and SKOV-3 EOC cells using short hairpin RNA (shRNA), an RNA interference strategy that could potentially overcome chemoresistance arising with angiogenic inhibitors. Unexpectedly, we observed an induction of more aggressive cellular behavior in transfected cells, leading to increased growth in mouse xenografts, enhanced accumulation of ascites, increased VEGF and neuropilin-1 (NRP-1) expression, and decreased expression of adhesion proteins, notably cadherins and integrins. Sonic hedgehog (SHH) pathways do not seem to be involved in the upregulation of NRP-1 message in VEGFR2 knockdown cells. Supporting our mouse model, we also found a significant increase in the ratio between NRP-1 and VEGFR2 with increasing tumor grade in 80 cases of human EOC. The change in EOC behavior that we report in this study occurred independent of the angiogenic response and shows the direct effect of VEGF blockade on the cancer cells themselves. Our findings highlight the possible confounding events that may affect the usefulness of RNAi in a therapeutic setting for disrupting EOC cell survival in ascites.

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“…EMT is a reversible dynamic process during which epithelial cells gradually adopt structural and functional characteristics of mesenchymal cells [10][11][12][13]. EMT is fundamental in several physiological processes, such as embryogenesis and wound healing.…”

mentioning

confidence: 99%

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Vaquero

Guedj

Clapéron

et al. 2017

Journal of Hepatology

111

115

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Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Unfortunately, most of the patients are not eligible for curative surgery owing to the presence of metastases at the time of diagnosis. Therefore, it is important to understand the steps leading to cell dissemination in patients with CCA. To metastasize from the primary site, cancer cells must acquire migratory and invasive properties by a cell plasticity-promoting phenomenon known as epithelial-mesenchymal transition (EMT). EMT is a reversible dynamic process by which epithelial cells gradually adopt structural and functional characteristics of mesenchymal cells, and has lately become a center of attention in the field of metastatic dissemination. In the present review, we aim to provide an extensive overview of the current clinical data and the prognostic value of different EMT markers that have been analyzed in CCA. We summarize all the regulatory networks implicated in EMT from the membrane receptors to the main EMT-inducing transcription factors (SNAIL, TWIST and ZEB). Furthermore, since a tumor is a complex structure not exclusively formed by tumor cells, we also address the prominent role of the main cell types of the desmoplastic stroma that characterizes CCA in the regulation of EMT. Finally, we discuss the therapeutic considerations and difficulties faced to develop an effective anti-EMT treatment due to the redundancies and bypasses among the pathways regulating EMT. 4Key Point Box -EMT is an early event of metastasis that endows tumor cells with invasive properties enabling them to spread toward other territories.-EMT contributes to CCA progression and chemoresistance.-The three families of transcription factors that regulate epithelial and mesenchymal marker expression during EMT (SNAIL, TWIST and ZEB) contribute to CCA progression.-Cells of CCA microenvironment, and not only cancer cells, lead to the activation of EMT.

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Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Cited by 197 publications

References 150 publications

Stromal myofibroblasts are drivers of invasive cancer growth

Stromal myofibroblasts are drivers of invasive cancer growth

Molecular blockade of VEGFR2 in human epithelial ovarian carcinoma cells

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

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