CXCL14, CXCR7 expression and CXCR4 splice variant ratio associate with survival and metastases in Ewing sarcoma patients

Sand, Laurens G.L.; Scotlandi, Katia; Berghuis, Dagmar; Snaar-Jagalska, B. Ewa; Picci, Piero; Schmidt, Thomas; Szuhai, Károly; Hogendoorn, Pancras C.W.

doi:10.1016/j.ejca.2015.08.020

Cited by 26 publications

(23 citation statements)

References 37 publications

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“…PRAS40 silencing induces the apoptosis of ES cells through regulating the insulin receptor/Akt and mTOR signaling pathways [119, 120]. The chemokine receptors CXCR4 and CXCR7 are expressed in ES, and their expression correlates with poor patient survival [121, 122]. EGR2 is a target gene of EWS-FLI1, and EGR2 knockdown inhibits ES cell proliferation, clonogenicity and spheroidal growth, and induces regression of ES xenografts [123, 124].…”

Section: Targeted Therapymentioning

confidence: 99%

Potential approaches to the treatment of Ewing's sarcoma

Guo

et al. 2016

Oncotarget

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Ewing’s sarcoma (ES) is a highly aggressive and metastatic tumor in children and young adults caused by a chromosomal fusion between the Ewing sarcoma breakpoint region 1 (EWSR1) gene and the transcription factor FLI1 gene. ES is managed with standard treatments, including chemotherapy, surgery and radiation. Although the 5-year survival rate for primary ES has improved, the survival rate for ES patients with metastases or recurrence remains low. Several novel molecular targets in ES have recently been identified and investigated in preclinical and clinical settings, and targeting the function of receptor tyrosine kinases (RTKs), the fusion protein EWS-FLI1 and mTOR has shown promise. There has also been increasing interest in the immune responses of ES patients. Immunotherapies using T cells, NK cells, cancer vaccines and monoclonal antibodies have been considered for ES, especially for recurrent patients. Because understanding the pathogenesis of ES is extremely important for the development of novel treatments, this review focuses on the mechanisms and functions of targeted therapies and immunotherapies in ES. It is anticipated that integrating the knowledge obtained from basic research and translational and clinical studies will lead to the development of novel therapeutic strategies for the treatment of ES.

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Section: Targeted Therapymentioning

confidence: 99%

Potential approaches to the treatment of Ewing's sarcoma

Guo

et al. 2016

Oncotarget

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“…There is growing evidence that cancer-related inflammation plays crucial roles in the process of tumorigenesis and progression in various malignant tumors, mainly via enhancing angiogenesis and metastasis, suppressing adaptive immune responses, and reducing reactions to chemotherapeutic drugs [14,15]. High expression of inflammation-related enzymes, proteins, or chemokine receptors in osteosarcoma has been already verified by various studies to correlate with poor outcomes, such as cyclooxygenase-2 (COX-2), matrix metalloproteinases (MMPs), heat shock proteins (HSPs), and chemokine (C-X-C motif) receptor 4 (CXCR4) [16][17][18][19][20]. In addition, the administration of anti-inflammatory drugs during chemotherapy has been confirmed to prolong patients' survival [21].…”

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confidence: 99%

Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma

et al. 2020

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Background: This study aimed to evaluate the clinical significance of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma. Methods: The clinical data of 133 osteosarcoma patients between January 2011 and February 2018 in our hospital was retrospectively collected and analyzed. NPS was calculated from four parameters, including serum albumin level, serum total cholesterol (TC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR). Patients were divided into three groups (group 1-3) based on NPS. The relationships between NPS and clinical features, overall survival (OS), and progression-free survival (PFS) were analyzed. Two prediction models based on NPS and clinical parameters were developed: clinical parameters model (model A), and the combined model of NPS and clinical parameters (model B). Their predictive performances were further evaluated and compared. Results: The median follow-up time of this cohort was 46.0 (range, 5-75) months, while the median OS and PFS was 40 (range, 5-75) months and 36 (range, 5-71) months, respectively. NPS was significantly correlated with gender, tumor location, Enneking stage, pathological fracture, local recurrence, and metastasis (all P < 0.05). Variables of NPS, Enneking stage, local recurrence, metastasis, and NLR were confirmed as independent prognostic factors for OS and PFS by univariate and multivariate Cox analysis. Prediction model B obtained larger AUCs for OS and PFS and showed better consistency between nomogram-predicted and actual survival than that of model A at the follow-up time of 1-, 3-, and 5-year. Conclusions: NPS was a novel, reliable, and multidimensional prognostic scoring system with favorable predictive performance for patients with osteosarcoma.

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“…In cancer cells, our group identified expression in a subset of melanoma cells (13). In addition, the two transcripts are expressed in Ewing sarcoma primary tissue and cell lines (40). It is not clear how common the expression of CXCR4A transcript is in cancer in general, and what is the potential impact of its expression.…”

Section: Discussionmentioning

confidence: 99%

Canonical and alternative transcript expression of PAX6 and CXCR4 in pancreatic cancer

et al. 2017

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Pancreatic cancer is a lethal disease with a propensity for invading and metastasizing into the surrounding tissues, including the liver and intestines. A number of factors are aberrantly overexpressed in this tumor type and actively promote cancer progression and metastasis. The present study demonstrates that paired box transcription factor 6 (PAX6) and C-X-C chemokine receptor 4 (CXCR4) are frequently co-expressed in primary pancreatic adenocarcinoma tumors and established cell lines. Expression analysis methods used in the present study included evaluation of protein expression by western blot analysis and immunofluorescence, transcript expression levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and luciferase assays utilizing regulatory elements from the CXCR4 gene locus. Canonical PAX6 and alternative splice variant PAX6(5a) proteins are expressed in pancreatic cancer and can drive gene expression through a conserved enhancer element within the first intron of the CXCR4 gene. As demonstrated by the introduction of an exogenous reporter construct with or without the intronic enhancer, loss of this element inhibited gene expression within numerous pancreatic cancer cell lines including Panc1, MIA-PaCa2 and BxPC3. All of the pancreatic cancer cell lines expressed the canonical CXCR4B transcript in addition to the alternatively spliced variant CXCR4A as determined by RT-qPCR experiments. The discovery of variant transcripts in pancreatic cancer cells may provide new candidates for future targeted therapies.

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CXCL14, CXCR7 expression and CXCR4 splice variant ratio associate with survival and metastases in Ewing sarcoma patients

Abstract: We identified a set of genes involved in CXCR4 signalling that may be used as a marker to predict survival and metastasis development in Ewing sarcoma.

Cited by 26 publications

References 37 publications

Potential approaches to the treatment of Ewing's sarcoma

Potential approaches to the treatment of Ewing's sarcoma

Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma

Canonical and alternative transcript expression of PAX6 and CXCR4 in pancreatic cancer

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