Cited by 176Adrenal and Paraganglionic TumorsGrowth Hormone and Insulin-like Growth FactorsAdrenal Hormones and Disorders

Expression of insulin-like growth factor-II and its receptor in pediatric and adult adrenocortical tumors

Almeida, Madson Q., Fragoso, Maria Candida Barisson Villares, Lotfi, Claudimara Ferini Pacicco, Santos, Mariza Gerdulo, Nishi, Mirian Yumie, Costa, Marcia Helena Soares, Lerario, Antonio Marcondes, Maciel, Carolina Canton +4 more·2008·The Journal of Clinical Endocrinology & Metabolism

Abstract

BACKGROUND: Adrenocortical tumors are heterogeneous neoplasms with incompletely understood pathogenesis. IGF-II overexpression has been consistently demonstrated in adult adrenocortical carcinomas. OBJECTIVES: The objective of the study was to analyze expression of IGF-II and its receptor (IGF-IR) in pediatric and adult adrenocortical tumors and the effects of a selective IGF-IR kinase inhibitor (NVP-AEW541) on adrenocortical tumor cells. PATIENTS: Fifty-seven adrenocortical tumors (37 adenomas and 20 carcinomas) from 23 children and 34 adults were studied. METHODS: Gene expression was determined by quantitative real-time PCR. Cell proliferation and apoptosis were analyzed in NCI H295 cells and a new cell line established from a pediatric adrenocortical adenoma. RESULTS: IGF-II transcripts were overexpressed in both pediatric adrenocortical carcinomas and adenomas. Otherwise, IGF-II was mainly overexpressed in adult adrenocortical carcinomas (270.5 +/- 130.2 vs. 16.1 +/- 13.3; P = 0.0001). IGF-IR expression was significantly higher in pediatric adrenocortical carcinomas than adenomas (9.1 +/- 3.1 vs. 2.6 +/- 0.3; P = 0.0001), whereas its expression was similar in adult adrenocortical carcinomas and adenomas. IGF-IR expression was a predictor of metastases in pediatric adrenocortical tumors in univariate analysis (hazard ratio 1.84; 95% confidence interval 1.28-2.66; P = 0.01). Furthermore, NVP-AEW541 blocked cell proliferation in a dose- and time-dependent manner in both cell lines through a significant increase of apoptosis. CONCLUSION: IGF-IR overexpression was a biomarker of pediatric adrenocortical carcinomas. Additionally, a selective IGF-IR kinase inhibitor had antitumor effects in adult and pediatric adrenocortical tumor cell lines, suggesting that IGF-IR inhibitors represent a promising therapy for human adrenocortical carcinoma.

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Crossref · 10.1210/jc.2008-0065

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  • In an NCI-H295 xenograft mouse model, IGF pathway inhibition by NVP-AEW541 and IMCA12 showed an antitumor effect.

    “In an NCI-H295 xenograft mouse model, IGF pathway inhibition by the small-molecule inhibitor NVP-AEW541 and the monoclonal IGF-1R antibody IMCA12 showed an antitumor effect.”

    From Adrenocortical carcinoma (2014) · cites this paper as [223]

  • Combined treatment of NCI-H295 cells with IGF-1R antagonists and mitotane resulted in a synergistic antiproliferative effect in vitro and in vivo.

    “Furthermore, the combined treatment of NCI-H295 cells with IGF-1R antagonists and mitotane resulted in a synergistic antiproliferative effect in vitro and in vivo in tumor xenografts (223, 227).”

    From Adrenocortical carcinoma (2014) · cites this paper as [223]

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Authors
Almeida, M. Q., Fragoso, M. C. B. V., Lotfi, C. F. P., Santos, M. G., Nishi, M. Y., Costa, M. H. S., Lerario, A. M., Maciel, C. C., Mattos, G. E., Jorge, A. A. L., Mendonca, B. B., & Latronico, A. C.
Affiliations
  • Universidade de São Paulo (BR)
  • Unidade de Endocrinologia do Desenvolvimento (M.Q.A., M.C.B.V.F., M.G.S., M.Y.N., M.H.S.C., A.M.L., A.A.L.J., B.B.M., A.C.L.), Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05403-900 São Paulo, Brazil
Corresponding author
Almeida, Madson Q.
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2008-09-01
Volume
93
Issue
9
Pages
3524-3531
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W2095417135
Cited by
176
References
49
Citations by year
2026: 4 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 10 · 2021: 6 · 2020: 13 · 2019: 6 · 2018: 11 · 2017: 5 · 2016: 10 · 2015: 12 · 2014: 17 · 2013: 7 · 2012: 17
FWCI
16.16
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
insulin-like growth factor II, IGF-II receptor, adrenocortical tumors, pediatric adrenocortical carcinoma, adrenal adenoma, NVP-AEW541, metastasis biomarkers, cell proliferation, apoptosis, cancer therapy
MeSH terms
Adenoma, Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Carcinoma, Child, Child, Preschool, Female, Humans, Infant, Insulin-Like Growth Factor II, Male, Middle Aged, Neoplasm Metastasis, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Receptor, IGF Type 2

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