Presence of Twist1-Positive Neoplastic Cells in the Stroma of Chromosome-Unstable Colorectal Tumors

Celesti, Giuseppe; Di, Giuseppe; Bianchi, Paolo; Grizzi, Fabio; Basso, Gianluca; Marchesi, Federica; Doni, Andrea; Marra, Giancarlo; Roncalli, Massimo; Mantovani, Alberto; Malesci, Alberto; Laghi, Luigi

doi:10.1053/j.gastro.2013.05.011

Cited by 51 publications

(46 citation statements)

References 42 publications

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“…In colorectal carcinoma, ZEB1-and Snail1-positive cells with a mesenchymal morphology at the invasive front showed strong nuclear b-catenin signals (due to an APC mutation), suggesting that colon carcinoma cells, but not stromal cells, have undergone EMT (Brabletz et al 2001(Brabletz et al , 2005Spaderna et al 2006). Recently, Celesti et al (2013) performed Twist1 immunostaining in combination with fluorescent in situ hybridization (FISH) analysis of chromosome translocation unique to human colorectal tumor cells and found that 17 out of 20 human colon tumors contained Twist1…”

Section: Clinical Evidence Of Emt In Primary Tumor Invasionmentioning

confidence: 99%

Epithelial–mesenchymal plasticity in carcinoma metastasis

2013

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Tumor metastasis is a multistep process by which tumor cells disseminate from their primary site and form secondary tumors at a distant site. Metastasis occurs through a series of steps: local invasion, intravasation, transport, extravasation, and colonization. A developmental program termed epithelial-mesenchymal transition (EMT) has been shown to play a critical role in promoting metastasis in epithelium-derived carcinoma. Recent experimental and clinical studies have improved our knowledge of this dynamic program and implicated EMT and its reverse program, mesenchymal-epithelial transition (MET), in the metastatic process. Here, we review the functional requirement of EMT and/or MET during the individual steps of tumor metastasis and discuss the potential of targeting this program when treating metastatic diseases.Epithelial and mesenchymal cell types have long been recognized by their unique cell morphology and organization in tissues. Epithelial cells form polarized sheets or layers of cells that are connected laterally via several types of cellular junctions, including adherens junctions, desmosomes, and tight junctions. In addition, epithelial cells anchor themselves to the underlying basement membrane via hemidesmosomes to maintain apical-basal polarity. Both desmosomes and hemidesmosomes further connect with the epithelial-specific cytokeratin intermediate filaments. In contrast, mesenchymal cells embed themselves inside the extracellular matrix (ECM) and rarely establish tight contact with neighboring cells. During specific embryonic morphogenesis processes such as mesoderm formation and neural crest development, epithelial cells can exhibit enormous plasticity and transit into a mesenchymal state by activating the epithelial-mesenchymal transition (EMT) program. After EMT, these cells lose their epithelial junctions and switch to producing vimentin filaments. The functional hallmark of the EMT program is to allow stationary epithelial cells to gain the ability to migrate and invade during developmental morphogenesis (Boyer and Thiery 1993;Hay 1995).Although epithelial cells convert into the mesenchymal state during developmental EMT, entering the EMT program is not necessarily an irreversible commitment, as evident during kidney tubule formation. These epithelial cells can activate a transitory EMT program and then undergo a reverse process called mesenchymal-epithelial transition (MET) to continue their differentiation paths (Thiery et al. 2009;Lim and Thiery 2012). In many instances, the identification of an epithelial versus a mesenchymal state can be relatively fluid, and a partial EMT/MET frequently occurs to fulfill unique developmental tasks. These dynamic EMT/MET events highlight the enormous flexibility of presumably differentiated cells during morphogenesis.In the past decade, an increasing number of studies have provided strong evidence for the reinitiation of the EMT developmental program in carcinoma progression and metastasis. This EMT program in tumor metastasis possesses many morpholog...

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Section: Clinical Evidence Of Emt In Primary Tumor Invasionmentioning

confidence: 99%

Epithelial–mesenchymal plasticity in carcinoma metastasis

2013

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“…Furthermore, a significant correlation has been reported between SLUG and vimentin expression, and upregulation of SLUG has emerged as an independent prognostic factor and a predictive marker of lymph node metastasis and sprouting angiogenesis in CRC patients [15,32]. Using TWIST1 immunostaining in combination with fluorescence in situ hybridization (FISH) analysis of the chromosome translocation unique to human CRC cells, it has been found that 17 out of 20 colon tumors contain TWIST1 + tumor cells with a mesenchymal phenotype [33]. In CRC patients, the TWIST1 overexpression is associated with nodal invasion, male sex and unfavorable outcomes [27,34,35].…”

Section: Transcriptional Regulation Of Emtmentioning

confidence: 99%

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

Cao

Liu

et al. 2015

Pathology - Research and Practice

321

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“…Immunostaining of CX 3 CL1 and CX 3 CR1 in tumor samples was evaluated by three independent operators, blind to any patient clinical data. Scores of CX 3 CL1 and CX 3 CR1 expression by tumor cells were calculated considering the percentage of positive tumor cells and staining intensity classified as negative (0), moderate (1), and strong (2). For each specimen, the entire section was analyzed and the final score was calculated using the following formula: ð0 3 % of negative tumor cellsÞþð1 3 % of moderate tumor cellsÞþð2 3 % of strong tumor cellsÞ 100 CD3 + and CD68 + cell density at the tumor invasive margin was measured in three randomly selected and noncontiguous microscopic areas encompassing the deep front of tumor invasion.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…After 24 h, cells were treated with 0.1 mM Fura-2 (Invitrogen) diluted in DMSO for 30 min. Subsequently, cells were incubated in a humidified atmosphere of 5% CO 2 and 95% air at 37˚C and monitored with a Cell-R IX81 microscopy (Olympus). At the indicated time point, 100 ng/ml rhCX 3 CL1 was added, and the variation in Fura-2 emission at 340 and 380 nm was analyzed in a time-lapse experiment (one image every 3 s) for the indicated time.…”

Section: Intracellular Calcium 2+ Influxmentioning

confidence: 99%

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The Fractalkine-Receptor Axis Improves Human Colorectal Cancer Prognosis by Limiting Tumor Metastatic Dissemination

Erreni

Siddiqui

Marelli

et al. 2016

The Journal of Immunology

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Human colorectal cancer (CRC) is a frequent neoplasia in Western countries, and its metastatic progression is a major cause of cancer-related death. In search of specific molecules upregulated in CRC, with possible clinical relevance, we performed a differential gene-profiling analysis in surgery-derived CRC samples and adjacent uninvolved intestinal mucosa. The chemokine CX3CL1 and its specific receptor CX3CR1 were significantly upregulated in tumors. Higher expression of CX3CL1 and CX3CR1 was confirmed by immunohistochemistry in 100 CRC tumor samples (stages I–III). Unexpectedly, high immune scores of CX3CL1 did not correlate with the density of tumor-infiltrating CD3+ T cells or CD68+ macrophages. Coexpression of ligand and receptor by tumor cells (axis-positive tumors) significantly associated with longer disease-free (p = 0.01) and disease-specific survival (p = 0.001). Conversely, axis-negative tumors (with low expression of both ligand and receptor) had increased risk of tumor relapse (p = 0.02), and increased likelihood of metachronous metastasis (p = 0.001), including after stage adjustment (p = 0.006). Transduction of CX3CL1 and CX3CR1 in CRC tumor cell lines induced cell aggregation that strongly inhibited in vitro migration in chemotaxis assays. In a mouse model of spleen–liver metastases, cancer dissemination to liver was dramatically reduced in CX3CL1-CX3CR1–expressing tumors, and ligand–receptor interaction was confirmed in cancer cells in vivo by fluorescence resonance energy transfer analysis. In conclusion, tumoral expression of the CX3CL1-CX3CR1 chemokine axis functions as a retention factor, increasing homotypic cell adhesion and limiting tumor spreading to metastatic sites. Lack or low levels of expression of CX3CL1-CX3CR1 by tumor cells identifies a group of CRC patients at increased risk of metastatic progression.

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Presence of Twist1-Positive Neoplastic Cells in the Stroma of Chromosome-Unstable Colorectal Tumors

Cited by 51 publications

References 42 publications

Epithelial–mesenchymal plasticity in carcinoma metastasis

Epithelial–mesenchymal plasticity in carcinoma metastasis

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

The Fractalkine-Receptor Axis Improves Human Colorectal Cancer Prognosis by Limiting Tumor Metastatic Dissemination

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