IGF2 role in adrenocortical carcinoma biology

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Pereira, SS (Author) ICBAS; Monteiro, M (Author) ICBAS; Costa, MM (Author) ICBAS; Moreira, A (Author) Other; Alves, MG (Author) Other; Oliveira, PF (Author) FMUP; Jarak, I (Author) Other; Pignatelli, D (Author) Other

Journal

The Journal is awaiting validation by the Administrative Services.

Title: ENDOCRINE

Vol. 66

Pages: 326-337

ISSN: 1355-008X

Publisher: Springer

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 12 Citations

Other information

Authenticus ID: P-00R-8XG

DOI: 10.1007/s12020-019-02033-5

Abstract (EN): Purpose Clinical outcomes of adrenocortical carcinomas (ACC) could be improved by using novel treatment targets based on the recent advances of tumor biology knowledge. Insulin-like growth factor 2 (IGF2) protein expression is usually 8-80 fold higher in ACC when compared to normal adrenal glands (N-AG) or adrenocortical adenomas (ACA), despite the fact that the biological features of high vs. low IGF2 expressing ACC have not yet been well characterized. Our goal was to understand the IGF2 role in ACC biology by focusing in several cancer hallmarks, including cell proliferation, viability, invasion, and metabolism. Methods IGF2 immunohistochemistry expression was evaluated in ACC (n = 13), non-functioning adrenocortical adenoma (ACAn) (n = 14), and N-AG (n = 9). The effects of IGF2 (50, 100 ng/mL) in cell proliferation, viability, invasion, and metabolism, as well as in MAPK/ERK and mTOR pathways activation and N-cadherin expression, were evaluated in the ACC human cell line H295R. Results IGF2 expression was increased in ACC compared to ACAn and N-AG. Exposure to 100 ng/mL of IGF2 increased H295R cell proliferation and viability. mTOR inhibition reverted IGF2 triggered cell proliferation and viability while MEK/ MAPK/ERK inhibition only reverted IGF2 effects on cell proliferation. IGF2 at a 50 ng/mL concentration increased the glycolytic flux and decreased glutamine consumption. Conclusions IGF2 is an excellent marker to differentiate ACC from ACAn. In addition, IGF2 was demonstrated to influence adrenocortical cancer cell proliferation, metabolism, and viability, but not the cell invasion. These data support that different IGF2 concentrations in ACC can be responsible for different biological behaviors of ACC.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12