Abstract
Neuroblastoma, a neural crest-derived childhood tumor of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. However, the majority of neuroblastomas are diagnosed as metastatic tumors with a poor prognosis despite intensive multimodal therapy. The neuropeptide somatostatin (SOM) has been shown to inhibit neuroblastoma growth and induce apoptosis in vitro. Therapeutic effects of SOM analogues are dependent on tumor expression of high-affinity receptors. In the present study, human neuroblastoma SH-SY5Y cells were grown as xenografts in nude rats. In vivo SOM receptor expression in the xenografts was identified using scintigraphy with 111In-pentetreotide. Rats were randomized to treatment with the long-acting SOM analogue octreotide (10 µg s.c. every 12 h), 13-cis-retinoic acid (4 mg orally every 24 h), or vasoactive intestinal peptide (40 µg s.c. every 24 h) and compared with controls. Tumor volume was assessed every second day and tumor weight after 10-12 d. Octreotide treatment inhibited neuroblastoma growth significantly with reduced tumor volumes at 10 and 12 d compared with untreated controls (mean 3.56 and 4.24 versus 6.48 and 8.01 mL, respectively; p < 0.01). Also, tumor weights after 10-12 d were reduced in octreotide-treated animals (n = 8, median weight 2.90 g, range 1.67-5.57 g) compared with untreated rats (n = 14, 7.54 g, 1.65-10.82 g, p = 0.005). Serum IGF-I decreased significantly over time both in rats treated with octreotide and in untreated controls. It is concluded that treatment with the SOM analogue octreotide may significantly decrease neuroblastoma tumor growth in vivo. Further studies are warranted to establish the role of SOM analogues in the treatment of children with unfavorable neuroblastoma.
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Abbreviations
- SOM:
-
somatostatin
- VIP:
-
vasoactive intestinal peptide
- SRS:
-
somatostatin receptor scintigraphy
References
Kogner P 1995 Neuropeptides in neuroblastomas and ganglioneuromas. In: Nyberg F, Sharma HS, Wiesenfeld-Hallin Z (eds) Progress in Brain Research, Vol 104, Neuropeptides in the Spinal Cord. Elsevier, Amsterdam, 325–338.
Reichlin S 1983 Somatostatin. N Engl J Med 309: 1495–1501.
Reichlin S 1983 Somatostatin. N Engl J Med 309: 1556–1563.
Shulkes A 1994 Somatostatin: physiology and clinical applications. Ballière Clin Endoc 8: 215–236.
Schally AV 1988 Oncological applications of somatostatin analogues. Cancer Res 48: 6977–6985.
Lamberts SWJ, van der Lely AJ, de Herder WW, Hofland LJ 1996 Octreotide. N Engl J Med 334: 246–254.
O'Dorisio MS, Chen F, O'Dorisio TM, Wray D, Qualman SJ 1994 Characterization of somatostatin receptors on human neuroblastoma tumors. Cell Growth Differ 5: 1–8.
Maggi M, Baldi E, Finetti G, Franceschelli F, Brocchi A, Lanzillotti R, Serio M, Camboniu MG, Thiele CJ 1994 Identification, characterization, and biological activity of somatostatin receptors in human neuroblastoma cell lines. Cancer Res 54: 124–133.
Candi E, Melino G, De Laurenzi V, Piacentini M, Guerrieri P, Spinedi A, Knight RA 1995 Tamoxifen and somatostatin affect tumors by inducing apoptosis. Cancer Lett 96: 141–145.
Moertel CL, Reubi JC, Scheithauer BS, Schaid DJ, Kvols LK 1994 Expression of somatostatin receptors in childhood neuroblastoma. Am J Clin Pathol 102: 752–756.
Krenning EP, Kwekkeboom DJ, Pauwels S, Kvols LK, Reubi JC 1995 Somatostatin receptor scintigraphy. Nucl Med Ann 1: 50
Sautter-Bihl ML, Dörr U, Schilling FH, Koscielniak E, Treuner J, Bihl H 1994 Somatostatin receptor imaging: a new horizon in the diagnostic management of neuroblastoma. Semin Oncol 21( suppl 13): 38–41.
Schilling FH, Ambros PF, Bihl H, Martinsson T, Ambros IM, Borgström P, Jacobson H, Falkmer UG, Treuner J, Kogner P 1999 Somatostatin receptor expression in vivo is absent in neuroblastoma showing distal deletion of chromosome 1p and di/tetraploid DNA content. Eur J Cancer ( in press)
Kogner P, Borgström P, Bjellerup P, Schilling FH, Refai E, Jonsson C, Dominici C, Wassberg E, Bihl H, Jacobsson H, Theodorsson E, Hassan M 1997 Somatostatin in neuroblastoma and ganglioneuroma. Eur J Cancer 33: 2084–2089.
Kälkner KM, Janson ET, Nilsson S, Carlsson S, Öberg K, Westlin JE 1995 Somatostatin receptor scintigraphy in patients with carcinoid tumors: comparison between radioligand uptake and tumor markers. Cancer Res 55( suppl 23): 5801s–5804s.
Mattson MEK, Enberg G, Ruusala AI, Hall K, Pählman S 1986 Mitogenic response of human SH-SY5Y neuroblastoma cells to insulin-like growth factor I and II is dependent on the stage of differentiation. J Cell Biol 102: 1949–1954.
Chanson P, Timsit J, Harris AG 1993 Clinical pharmacokinetics of octreotide. Therapeutic applications in patients with pituitary tumors. Clin Pharmacokinet 25: 375–391.
Albers AR, O'Dorisio MS 1996 Clinical use of somatostatin analogues in paediatric oncology. Digestion 57( suppl 1): 38–41.
Kogner P, Theodorsson E, Björk O 1993 Neuropeptides indicating growth, differentiation, and outcome in childhood neuroblastoma and ganglioneuroma. Clin Chem Enzyme Comms 5: 289–294.
Bjellerup P, Theodorsson E, Kogner P 1995 Somatostatin and vasoactive intestinal peptide (VIP) in neuroblastoma and ganglioneuroma: chromatographic characterisation and release during surgery. Eur J Cancer 31A: 481–485.
Biedler J, Helson L, Spengler BA 1973 Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res 33: 2643–2652.
Wassberg E, Påhlman S, Westlin JE, Christofferson R 1997 The angiogenesis inhibitor TNP-470 reduces the growth rate of human neuroblastoma is nude rats. Pediatr Res 41: 327–333.
Bang P, Eriksson U, Sara V, Wivall IL, Hall K 1991 Comparison of acid ethanol extraction and gel filtration prior to IGF-I and IGF-II radioimmunoassays: improvement of determinations in acid ethanol extracts by use of truncated IGF-I as radioligand. Acta Endocrinol (Copenh) 124: 620–629.
Hassan M, Refai E, Andersson M, Schnell PO, Jacobsson H 1994 In vivo dynamical distribution of 131I-VIP in the rat studied by gamma-camera. Nucl Med Biol 21: 865–872.
Sidell N 1982 Retinoic acid-induced growth inhibition and morphologic differentiation of human neuroblastoma cells in vitro. J Natl Cancer Inst 68: 589–596.
Reynolds CP, Kane DJ, Einhorn PA, Matthay KK, Crouse VL, Wilbur JR, Shurin SB, Seeger RC 1991 Response of neuroblastoma to retinoic acid in vitro and in vivo. Prog Clin Biol Res 366: 203–211.
Cornaglia Ferraris P, Marottini GL, Ponzoni M 1992 Gamma-interferon and retinoic acid synergize in inhibiting the growth of human neuroblastoma cells in nude mice. Cancer Lett 61: 215–220.
Abemayor E 1992 The effects of retinoic acid on the in vitro and in vivo growth of neuroblastoma cells. Laryngoscope 102: 1133–1149.
Pence JC, Shorter NA 1993 The autocrine function of vasoactive intestinal peptide on human neuroblastoma cell growth and differentiation. Arch Surg 128: 591–595.
Jansson ET, Westlin JE, Eriksson B, Ahlström H, Nilsson S, Öberg K 1994 (111In-DTPA-D-Phe1) octreotide scintigraphy in patients with carcinoid tumors: the predictive value for somatostatin analogue treatment. Eur J Endocrinol 131 J Endocrinol 131: 577–581.
Hillman N, Herranz L, Alvarez C, Martinez Olmos MA, Marco A, Gomes-Pan A 1998 Efficacy of octreotide in the regression of a metastatic carcinoid tumor despite negative imaging with In-111-pentetreotide. Exp Clin Endocrinol Diabetes 106: 226–230.
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Supported by the Swedish Children's Cancer Foundation, Swedish Cancer Society, and research funds of the Karolinska Institute.
This work was presented in part as an oral presentation at Advances in Neuroblastoma Research 1998, Bath, UK, June 15-17, 1998, and awarded the Evans Prize.
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Borgström, P., Hassan, M., Wassberg, E. et al. The Somatostatin Analogue Octreotide Inhibits Neuroblastoma Growth in Vivo. Pediatr Res 46, 328–332 (1999). https://doi.org/10.1203/00006450-199909000-00014
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DOI: https://doi.org/10.1203/00006450-199909000-00014
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