A Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma

Dvorkina, M., Nieddu, V., Chakelam, S., Pezzolo, A., Cantilena, S., Leite, A.P., Chayka, O., Regad, T., Pistorio, A., Sementa, A.R., Virasami, A., Barton, A., Montano, X., Lechertier, T., Brindle, N., Morgenstern, D., Lebras, M., Burns, A.J., Saunders N.J., Hodivala-Dilke, K., Bagella, L., De The, H., Anderson, J., Sebire, N., Pistoia, V., Sala, A. and Salomoni, P. 2016. A Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma. Clinical Cancer Research. 22 (13), pp. 3398-3409. https://doi.org/10.1158/1078-0432.CCR-15-2081

TitleA Promyelocytic Leukemia Protein-Thrombospondin-2 Axis and the Risk of Relapse in Neuroblastoma
TypeJournal article
AuthorsDvorkina, M., Nieddu, V., Chakelam, S., Pezzolo, A., Cantilena, S., Leite, A.P., Chayka, O., Regad, T., Pistorio, A., Sementa, A.R., Virasami, A., Barton, A., Montano, X., Lechertier, T., Brindle, N., Morgenstern, D., Lebras, M., Burns, A.J., Saunders N.J., Hodivala-Dilke, K., Bagella, L., De The, H., Anderson, J., Sebire, N., Pistoia, V., Sala, A. and Salomoni, P.
Abstract

Purpose: Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system with a complex biology, prone to metastasize and relapse. High-risk, metastatic cases are explained in part by amplification or mutation of oncogenes, such as MYCN and ALK, and loss of tumor suppressor genes in chromosome band 1p. However, it is fundamental to identify other pathways responsible for the large portion of neuroblastomas with no obvious molecular alterations.

Experimental Design: Neuroblastoma cell lines were used for the assessment of tumor growth in vivo and in vitro. Protein expression in tissues and cells was assessed using immunofluorescence and IHC. The association of promyelocytic leukemia (PML) expression with neuroblastoma outcome and relapse was calculated using log-rank and Mann–Whitney tests, respectively. Gene expression was assessed using chip microarrays.

Results: PML is detected in the developing and adult sympathetic nervous system, whereas it is not expressed or is low in metastatic neuroblastoma tumors. Reduced PML expression in patients with low-risk cancers, that is, localized and negative for the MYCN proto-oncogene, is strongly associated with tumor recurrence. PML-I, but not PML-IV, isoform suppresses angiogenesis via upregulation of thrombospondin-2 (TSP2), a key inhibitor of angiogenesis. Finally, PML-I and TSP2 expression inversely correlates with tumor angiogenesis and recurrence in localized neuroblastomas.

Conclusions: Our work reveals a novel PML-I–TSP2 axis for the regulation of angiogenesis and cancer relapse, which could be used to identify patients with low-risk, localized tumors that might benefit from chemotherapy.

KeywordsPromyelocytic Leukemia Protein–Thrombospondin-2 Axis, neuroblastoma
JournalClinical Cancer Research
Journal citation22 (13), pp. 3398-3409
ISSN1078-0432
Year2016
PublisherAmerican Association for Cancer Research
Digital Object Identifier (DOI)https://doi.org/10.1158/1078-0432.CCR-15-2081
PubMed ID27076624
Web address (URL)https://www.ncbi.nlm.nih.gov/pubmed/27076624
Publication dates
Published13 Apr 2016

Related outputs

Preprint: SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB as potential prognostic and infection biomarkers in neuroblastoma
Brandon Bergsneider, Elise Bailey, Yusuf Ahmed, Namrata Gogineni, Derek Huntley and Ximena Montano 2024. Preprint: SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB as potential prognostic and infection biomarkers in neuroblastoma. Authorea. https://doi.org/10.22541/au.170666000.06060674/v1

A Potential Prognostic Gene Signature Associated with p53-Dependent NTRK1 Activation and Increased Survival of Neuroblastoma Patients
Currie, David, Wong, Nicole, Zane, Isabelle, Rix, Tom, Vardakastanis, Marios, Claxton, Amelia, Ong, Karine K. V., Macmorland, William, Poivet, Arthur, Brooks, Anthony, Niola, Paola, Huntley, Derek and Montano, Ximena 2024. A Potential Prognostic Gene Signature Associated with p53-Dependent NTRK1 Activation and Increased Survival of Neuroblastoma Patients. Cancers. 16 (4) 722. https://doi.org/10.3390/cancers16040722

Analysis of SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB in datasets from non SARS-CoV-2 infected neuroblastoma patients, as potential prognostic and infection biomarkers in neuroblastoma
Bergsneider, B., Bailey, E., Ahmed, Y., Gogineni, N., Huntley, D. and Montano Hernandez, X. 2021. Analysis of SARS-CoV-2 infection associated cell entry proteins ACE2, CD147, PPIA, and PPIB in datasets from non SARS-CoV-2 infected neuroblastoma patients, as potential prognostic and infection biomarkers in neuroblastoma. Biochemistry and Biophysics Reports. 27 101081. https://doi.org/10.1016/j.bbrep.2021.101081

The presence of Y674/Y675 phosphorylated NTRK1 via TP53 repression of PTPN6 expression as a potential prognostic marker in neuroblastoma
Youssef, G., Gillett, C., Rampling, D., Chagtai, T., Virasami, A., Barton, J., Edwards, D., Sebire, N., Anderson, J. and Montano, X. 2019. The presence of Y674/Y675 phosphorylated NTRK1 via TP53 repression of PTPN6 expression as a potential prognostic marker in neuroblastoma. Human Pathology. 86, pp. 182-192. https://doi.org/10.1016/j.humpath.2018.12.003

Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: a potential novel prognostic marker for breast cancer
Youssef, G., Gillett, C., Agbaje, O., Crompton, T. and Montano Hernandez, X. 2014. Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of PTPN6 expression: a potential novel prognostic marker for breast cancer. Modern Pathology. 27, pp. 361-374 23948750. https://doi.org/10.1038/modpathol.2013.129

Repression of SHP-1 Expression by p53 leads to trkA Tyrosine Phosphorylation and Suppression of Breast Cancer Cell Proliferation
Montano, Ximena 2009. Repression of SHP-1 Expression by p53 leads to trkA Tyrosine Phosphorylation and Suppression of Breast Cancer Cell Proliferation. Oncogene. 28, pp. 3787-3800. https://doi.org/10.1038/onc.2009.143

Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated Na+ channel activity
Ding, Y., Brackenbury, W.J., Uysal Onganer, P., Montano, Ximena, Porter, L.M., Bates, L.F. and Djamgoz, M.B.A. 2008. Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated Na+ channel activity. Journal of Cellular Physiology. 215 (1), pp. 77-81. https://doi.org/10.1002/jcp.21289

Epidermal growth factor, neurotrophins and the metastatic cascade in prostate cancer
Montano, Ximena and Djamgoz, Mustafa B.A. 2004. Epidermal growth factor, neurotrophins and the metastatic cascade in prostate cancer. FEBS Letters. 571, pp. 1-3. https://doi.org/10.1016/j.febslet.2004.06.088

Analysis of trk A tyrosine kinase and p53 association
Browes, C., Rowe, J., Brown, A. and Montano, Ximena 2001. Analysis of trk A tyrosine kinase and p53 association. FEBS Letters. 497, pp. 20-25. https://doi.org/10.1016/s0014-5793(01)02429-2

Common amino acid sequence motifs in p53, 14-3-3 and Akt protein families
Montano, Ximena 2001. Common amino acid sequence motifs in p53, 14-3-3 and Akt protein families. FEBS Letters. 507 (2), pp. 237-240. https://doi.org/10.1016/S0014-5793(01)02903-9

c-abl is involved in the association of p53 and trk A
Montano, Ximena 2000. c-abl is involved in the association of p53 and trk A. Oncogene. 19, pp. 3032-3040. https://doi.org/10.1038/sj.onc.1203619

Permalink - https://westminsterresearch.westminster.ac.uk/item/qwz9y/a-promyelocytic-leukemia-protein-thrombospondin-2-axis-and-the-risk-of-relapse-in-neuroblastoma


Share this

Usage statistics

118 total views
1 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.