Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors

Barry, S., Carlsen, E., Marques, P., Stiles, C., Gadaleta, E., Berney, D., Roncaroli, F., Chelala, C., Solomou, A., Herincs, M., Caimari, F., Grossman, A., Crnogorac-Jurcevic, T., Haworth, O., Gaston-Massuet, C. and Korbonits, M. 2019. Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors. Oncogene. 38, pp. 5381-5395. https://doi.org/10.1038/s41388-019-0779-5

TitleTumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors
TypeJournal article
AuthorsBarry, S., Carlsen, E., Marques, P., Stiles, C., Gadaleta, E., Berney, D., Roncaroli, F., Chelala, C., Solomou, A., Herincs, M., Caimari, F., Grossman, A., Crnogorac-Jurcevic, T., Haworth, O., Gaston-Massuet, C. and Korbonits, M.
Abstract

The molecular mechanisms leading to aryl hydrocarbon receptor interacting protein (AIP) mutation-induced aggressive, young-onset growth hormone-secreting pituitary tumors are not fully understood. In this study, we have identified that AIP-mutation-positive tumors are infiltrated by a large number of macrophages compared to sporadic tumors. Tissue from pituitary-specific Aip-knockout (AipFlox/Flox;Hesx1Cre/+) mice recapitulated this phenotype. Our human pituitary tumor transcriptome data revealed the "epithelial-to-mesenchymal transition (EMT) pathway" as one of the most significantly altered pathways in AIPpos tumors. Our in vitro data suggest that bone marrow-derived macrophage-conditioned media induces more prominent EMT-like phenotype and enhanced migratory and invasive properties in Aip-knockdown somatomammotroph cells compared to non-targeting controls. We identified that tumor-derived cytokine CCL5 is upregulated in AIP-mutation-positive human adenomas. Aip-knockdown GH3 cell-conditioned media increases macrophage migration, which is inhibited by the CCL5/CCR5 antagonist maraviroc. Our results suggest that a crosstalk between the tumor and its microenvironment plays a key role in the invasive nature of AIP-mutation-positive tumors and the CCL5/CCR5 pathway is a novel potential therapeutic target.

KeywordsAIP, pituitary tumors, microenvironment
JournalOncogene
Journal citation38, pp. 5381-5395
ISSN0950-9232
Year2019
PublisherNature Publishing Group
Publisher's version
Digital Object Identifier (DOI)https://doi.org/10.1038/s41388-019-0779-5
Publication dates
Published12 Mar 2019
FunderWellcome Trust
LicenseCC BY 4.0

Related outputs

AIP: A double agent? The tissue-specific role of AIP as a tumour suppressor or as an oncogene.
Haworth, Oliver and Korbonits, M. 2022. AIP: A double agent? The tissue-specific role of AIP as a tumour suppressor or as an oncogene. British Journal of Cancer. 127, pp. 1175-1176. https://doi.org/10.1038/s41416-022-01964-7

Aryl Hydrocarbon Receptor Interacting Protein Maintains Germinal Center B Cells through Suppression of BCL6 Degradation
Sun, D., Stopka-Farooqui, U., Barry, S., Aksoy, E., Parsonage, G., Vossenkämper, A., Capasso, M., Wan, X., Norris, S., Marshall, J., Clear, A., Gribben, J., MacDonald, T., Buckley, C., Korbonits, M. and Haworth, O. 2019. Aryl Hydrocarbon Receptor Interacting Protein Maintains Germinal Center B Cells through Suppression of BCL6 Degradation. Cell Reports. 27, pp. 1461-1471. https://doi.org/10.1016/j.celrep.2019.04.014

Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis
Norling, L., Headland, S., Dalli, J., Arnardottir, H., Haworth, O., Jones, H., Irimia, D., Serhan, C. and Perretti, M. 2016. Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis. JCI Insight. 1 (5), p. e85922 e85922. https://doi.org/10.1172/jci.insight.85922

Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation
Talbot, S., Abdulnour, R., Burkett, P., Lee, S., Cronin, S., Pascal, M., Laedermann, C., Foster, S., Tran, J., Lai, N., Chiu, I., Ghasemlou, N., DiBiase, M., Roberson, D., Von Hehn, C., Agac, B., Haworth, O., Seki, H., Penninger, J., Kuchroo, V., Bean, B., Levy, B. and Woolf, C. 2015. Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation. Neuron. 87 (2), pp. 341-354. https://doi.org/10.1016/j.neuron.2015.06.007

Permalink - https://westminsterresearch.westminster.ac.uk/item/qwy43/tumor-microenvironment-defines-the-invasive-phenotype-of-aip-mutation-positive-pituitary-tumors


Share this

Usage statistics

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