This Article Full Text Full Text (PDF) Correction (v67,p1877) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vitale, G. Articles by Hofland, L. J. Search for Related Content PubMed PubMed Citation Articles by Vitale, G. Articles by Hofland, L. J.

IFN-ß Is a Highly Potent Inhibitor of Gastroenteropancreatic Neuroendocrine Tumor Cell Growth In vitro

¹ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; ² Department of Immunology, Berlex Bioscience, Inc., Richmond, Richmond, California; and ³ Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples, Naples, Italy

Requests for reprints: Giovanni Vitale, Department of Internal Medicine, Erasmus Medical Center, Room EE 585d, Dr. Molewaterplein 50, 3015 GE Rotterdam, the Netherlands. Phone: 31-10-4635952; Fax: 31-10-4635430; E-mail: vanni10{at}yahoo.com.

IFN- 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-ß, has not been evaluated. We compared the antitumor effects of IFN- and IFN-ß 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-ß 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- resulted significantly in a less potent effect (IC₅₀: 44 IU/mL, maximal inhibition: 26%). IFN- induced only cell cycle arrest, with an accumulation of the cells in S phase. IFN-ß, 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-ß severely suppressed chromogranin A levels in the medium from BON cells after 6 days of treatment. In conclusion, IFN-ß is much more potent, compared with IFN-, 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-ß has comparable potent tumor growth inhibitory effects in vivo. (Cancer Res 2006; 66(1): 554-62)

This article has been cited by other articles:

				P. J. D. Delhanty, P. M. van Koetsveld, C. Gauna, B. van de Zande, G. Vitale, L. J. Hofland, and A. J. van der Lely Ghrelin and its unacylated isoform stimulate the growth of adrenocortical tumor cells via an anti-apoptotic pathway Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E302 - E309. [Abstract] [Full Text] [PDF]

				K. Zitzmann, S. Brand, E. N. De Toni, S. Baehs, B. Goke, J. Meinecke, G. Spottl, H. H.H.D. Meyer, and C. J. Auernhammer SOCS1 Silencing Enhances Antitumor Activity of Type I IFNs by Regulating Apoptosis in Neuroendocrine Tumor Cells Cancer Res., May 15, 2007; 67(10): 5025 - 5032. [Abstract] [Full Text] [PDF]

				K. H. Weylandt, M. Nebrig, N. Jansen-Rosseck, J. S. Amey, D. Carmena, B. Wiedenmann, C. F. Higgins, and A. Sardini ClC-3 expression enhances etoposide resistance by increasing acidification of the late endocytic compartment Mol. Cancer Ther., March 1, 2007; 6(3): 979 - 986. [Abstract] [Full Text] [PDF]

				Correction: Type I IFNs and Carcinoids Cancer Res., February 15, 2007; 67(4): 1877 - 1877. [Full Text] [PDF]

				R. Benjamin, A. Khwaja, N. Singh, J. McIntosh, A. Meager, M. Wadhwa, C. Streck, C. Ng, A. M. Davidoff, and A. C. Nathwani Continuous delivery of human type I interferons ({alpha}/{beta}) has significant activity against acute myeloid leukemia cells in vitro and in a xenograft model Blood, February 1, 2007; 109(3): 1244 - 1247. [Abstract] [Full Text] [PDF]

				N Fazio, F de Braud, G Delle Fave, and K Oberg Interferon-{alpha} and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination? Ann. Onc., January 1, 2007; 18(1): 13 - 19. [Abstract] [Full Text] [PDF]

				P. M. van Koetsveld, G. Vitale, W. W. de Herder, R. A. Feelders, K. van der Wansem, M. Waaijers, C. H. J. van Eijck, E.-J. M. Speel, E. Croze, A.-J. van der Lely, et al. Potent Inhibitory Effects of Type I Interferons on Human Adrenocortical Carcinoma Cell Growth J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4537 - 4543. [Abstract] [Full Text] [PDF]