IFN-β is a highly potent inhibitor of gastroenteropancreatic neuroendocrine tumor cell growth in vitro

Giovanni Vitale, Wouter W. De Herder, Peter M. Van Koetsveld, Marlijn Waaijers, Wenda Schoordijk, Ed Croze, Annamaria Colao, Steven W J Lamberts, Leo J. Hofland

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Abstract

IFN-α controls hormone secretion and symptoms in human gastroenteropancreatic neuroendocrine tumors (GEP-NET) but it rarely induces a measurable tumor size reduction. The effect of other type I IFNs, e.g., IFN-β, has not been evaluated. We compared the antitumor effects of IFN-α and IFN-β in BON cells, a functioning human GEP-NET cell line. As determined by quantitative reverse transcription-PCR analysis and immunocytochemistry, BON cells expressed the active type I IFN receptor mRNA and protein (IFNAR-1 and IFNAR-2c subunits). After 3 and 6 days of treatment, IFN-β significantly inhibited BON cell growth in a time- and dose-dependent manner. IC50 and maximal inhibitory effect on day 6 were 8 IU/mL and 98%, respectively. In contrast, the effect of IFN-α resulted significantly in a less potent effect (IC50: 44 IU/mL, maximal inhibition: 26%). IFN-α induced only cell cycle arrest, with an accumulation of the cells in S phase. IFN-β, apart from a more potent delay in S-G2-M phase transit of the cell cycle, also induced a strong stimulation of apoptosis, evaluated by flow cytometry (Annexin V and 7-AAD) and measurement of the DNA fragmentation. Besides, only IFN-β severely suppressed chromogranin A levels in the medium from BON cells after 6 days of treatment In conclusion, IFN-β is much more potent, compared with IFN-α, in its inhibitory effect on GEP-NET cell proliferation in vitro through the induction of apoptosis and cell cycle arrest. Further studies are required to establish whether IFN-β has comparable potent tumor growth inhibitory effects in vivo.

Original languageEnglish
Pages (from-to)554-562
Number of pages9
JournalCancer Research
Volume66
Issue number1
DOIs
Publication statusPublished - Jan 1 2006

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Neuroendocrine Cells
Growth
Cell Cycle Checkpoints
Inhibitory Concentration 50
Apoptosis
Chromogranin A
G2 Phase
Annexin A5
DNA Fragmentation
Tumor Cell Line
S Phase
Cell Division
Reverse Transcription
Neoplasms
Cell Cycle
Flow Cytometry
Immunohistochemistry
Cell Proliferation
In Vitro Techniques
Gastro-enteropancreatic neuroendocrine tumor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vitale, G., De Herder, W. W., Van Koetsveld, P. M., Waaijers, M., Schoordijk, W., Croze, E., ... Hofland, L. J. (2006). IFN-β is a highly potent inhibitor of gastroenteropancreatic neuroendocrine tumor cell growth in vitro. Cancer Research, 66(1), 554-562. https://doi.org/10.1158/0008-5472.CAN-05-3043

IFN-β is a highly potent inhibitor of gastroenteropancreatic neuroendocrine tumor cell growth in vitro. / Vitale, Giovanni; De Herder, Wouter W.; Van Koetsveld, Peter M.; Waaijers, Marlijn; Schoordijk, Wenda; Croze, Ed; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J.

In: Cancer Research, Vol. 66, No. 1, 01.01.2006, p. 554-562.

Research output: Contribution to journalArticle

Vitale, G, De Herder, WW, Van Koetsveld, PM, Waaijers, M, Schoordijk, W, Croze, E, Colao, A, Lamberts, SWJ & Hofland, LJ 2006, 'IFN-β is a highly potent inhibitor of gastroenteropancreatic neuroendocrine tumor cell growth in vitro', Cancer Research, vol. 66, no. 1, pp. 554-562. https://doi.org/10.1158/0008-5472.CAN-05-3043
Vitale, Giovanni ; De Herder, Wouter W. ; Van Koetsveld, Peter M. ; Waaijers, Marlijn ; Schoordijk, Wenda ; Croze, Ed ; Colao, Annamaria ; Lamberts, Steven W J ; Hofland, Leo J. / IFN-β is a highly potent inhibitor of gastroenteropancreatic neuroendocrine tumor cell growth in vitro. In: Cancer Research. 2006 ; Vol. 66, No. 1. pp. 554-562.
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AU - Schoordijk, Wenda

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