Influence of hypoxia-dependent factors on the progression of neuroblastoma

Ameis, Helen M.; Drenckhan, Astrid; Freytag, Morton; Izbicki, Jakob R.; Supuran, Claudiu T.; Reinshagen, Konrad; Holland‐Cunz, Stefan; Gros, Stephanie J.

doi:10.1007/s00383-015-3831-8

Cited by 14 publications

(18 citation statements)

References 37 publications

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“…We could recently show that CAIX expression in neuroblastoma cell lines is hypoxia-dependent and these cells are responsive to anti-CAIX treatment in vivo 8 . Our research indicates that PGK1 together with CXCR4 enhances metastases and that the presence of high CAIX expression is a negative prognostic factor in neuroblastoma patients 8 , 9 . A similar hypoxia-dependent expression of CAIX has been described for many solid tumours including esophageal cancer 6 , 7 , 10 .…”

Section: Introductionmentioning

confidence: 59%

CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target

Drenckhan

Freytag

Supuran

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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The hypoxic tumour microenvironment of solid tumours represents an important starting point for modulating progression and metastatic spread. Carbonic anhydrase IX (CAIX) is a known HIF-1α-dependent key player in maintaining cell pH conditions under hypoxia. We show that CAIX is strongly expressed in esophageal carcinoma tissues. We hypothesize that a moderate CAIX expression facilitates metastases and thereby worsens prognosis. Selective inhibition of CAIX by specific CAIX inhibitors and a CAIX knockdown effectively inhibit proliferation and migration in vitro. In the orthotopic esophageal carcinoma model, the humanized HER2 antibody trastuzumab down-regulates CAIX, possibly through CAIX’s linkage with HER2 in the hypoxic microenvironment. Our results show CAIX to be an essential part of the tumour microenvironment and a possible master regulator of tumour progression. This makes CAIX a highly effective and feasible therapeutic target for selective cancer treatment.

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Section: Introductionmentioning

confidence: 59%

CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target

Drenckhan

Freytag

Supuran

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…NB-hop genes are known from the literature to be modulated by hypoxia and encode proteins that are involved in key biological processes associated with the response to hypoxia [3,17,[101][102][103][104][105][106][107][108][109]. Expression of these genes has been previously reported to represent a marker of hypoxia in NB cell lines [3,102,105] and tumors [102], and to correlate with NB bone marrow metastases and poor patient outcome [3,101]. The expression of NB-hop genes correlates with HIF-1a expression, which is one of the most important regulators of the cellular response to hypoxia [16].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming

Cangelosi

Morini

Zanardi

et al. 2020

Cancers

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The biological and clinical heterogeneity of neuroblastoma (NB) demands novel biomarkers and therapeutic targets in order to drive the most appropriate treatment for each patient. Hypoxia is a condition of low-oxygen tension occurring in poorly vascularized tumor tissues. In this study, we aimed to assess the role of hypoxia in the pathogenesis of NB and at developing a new clinically relevant hypoxia-based predictor of outcome. We analyzed the gene expression profiles of 1882 untreated NB primary tumors collected at diagnosis and belonging to four existing data sets. Analyses took advantage of machine learning methods. We identified NB-hop, a seven-gene hypoxia biomarker, as a predictor of NB patient prognosis, which is able to discriminate between two populations of patients with unfavorable or favorable outcome on a molecular basis. NB-hop retained its prognostic value in a multivariate model adjusted for established risk factors and was able to additionally stratify clinically relevant groups of patients. Tumors with an unfavorable NB-hop expression showed a significant association with telomerase activation and a hypoxic, immunosuppressive, poorly differentiated, and apoptosis-resistant tumor microenvironment. NB-hop defines a new population of NB patients with hypoxic tumors and unfavorable prognosis and it represents a critical factor for the stratification and treatment of NB patients.

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“…Functionally, genes such as NOTCH2, PGK1, and BUB1 have been reported to promote or suppress the neuroblastoma progression. 33 - 35 Prognostically, PGK1 was identified as a predictor of neuroblastoma outcome. 36 …”

Section: Discussionmentioning

confidence: 99%

Comprehensive Characterization of Circular RNAs in Neuroblastoma Cell Lines

Zhang

Zhou

et al. 2020

Technol Cancer Res Treat

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Neuroblastoma (NB) is a rare type of cancer but frequently occurred in children. However, it is still unclear whether circular RNAs (circRNAs) play key roles in NB tumorigenesis or progression. In this study, we identified 39,022 circRNAs across the 39 neuroblastoma and 2 normal cell lines. With the gene and circRNA expression data, we classified the NB cell lines, identified and characterized the functional circRNAs in the 3 NB classes. Specifically, 29 circRNAs were found to be dysregulated in the NB classes. Notably, 7 circRNAs located within MYCN-amplified regions were upregulated in cell lines with the high activities of MYC targets and MYCN amplification, and were highly correlated with expression of their parental gene, NBAS. Subsequently, we constructed ceRNA networks for the functional circRNAs. Specifically, hsa_circ_0005379 was identified as a critical regulator in the ceRNA networks because of targeting 13 genes, which formed a complex competing endogenous RNA (ceRNA) network. Moreover, hsa_circ_0002343, which was connected with few genes, might regulate the PI3K/Akt/mTOR signaling via RAC1. Furthermore, 3 genes, including NOTCH2, SERPINH1, and LAMC1, involved in epithelial mesenchymal transition (EMT) were observed to connect with hsa_circ_0001361, suggesting that this circRNA was closely associated with EMT. Consequently, 7 genes, such as DAD1, PPIA, NOTCH2, PGK1, BUB1, EIF2S1, and TCF7L2, were found to be closely associated with both event-free survival (EFS) and overall survival (OS). In conclusion, the present study identified functional circRNAs and predicted their functionality in neuroblastoma cell lines, which not only improved the understanding of circRNAs in neuroblastoma, but also provided the evidences for the related researchers.

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Influence of hypoxia-dependent factors on the progression of neuroblastoma

Abstract: Our results show that the hypoxic factors in the tumour`s microenvironment further the progression of tumour disease. This strengthens the perspectives for additive novel therapeutic approaches targeting hypoxia-dependent factors in this childhood disease.

Cited by 14 publications

References 37 publications

CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target

CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target

Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming

Comprehensive Characterization of Circular RNAs in Neuroblastoma Cell Lines

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