G. Prevost et al., SOMATOSTATIN-14 MAINLY BINDS THE SOMATOSTATIN RECEPTOR SUBTYPE-2 IN HUMAN NEUROBLASTOMA TUMORS, Neuroendocrinology, 63(2), 1996, pp. 188-197
Neuroblastoma is a pediatric cancer for which a cure is elusive for mo
st children with disseminated disease. Neuroblastomas possess receptor
s for somatostatin (SS). Some SS analogues can inhibit their prolifera
tion. In addition, when SS analogues were used as agents for scintigra
phy, neuroblastoma tumor sites can be localized with high efficiency.
In this study, to better characterize the SS receptor subtype(s) (sst1
-5) present in primary tumors and metastases of neuroblastoma, we show
that: (1) The ligand I-125-Tyr(11)-SS-14 binding on membrane proteins
from primary tumors and metastases of neuroblastoma cell line IGR-N-9
1 developed in nude mice shows similar values of Kd (in order of 0.1 n
M) and B-max (in order of fmol/mg) by filter-retention assay. These da
ta are close to those measured on two other neuroblastoma cell lines:
SK-N-SH and IGR-N-835 or to that measured on the rat cerebral cortex.
(2) The IGR-N-91 sublines derived from primary tumor and metastases sh
ow one major complex of 57 kD by the chemical cross-linking assay usin
g the ligands: I-125-SS-14 and I-125-BIM23014. One similar major compl
ex of 57 kD was also detected in SK-N-SH and IGR-N-835 or in the cereb
ral cortex. (3) Addition of excess nonlabeled peptides selective for s
st2 (BIM23014, BIM23060, BIM23068) suppressed the formation of the com
plex 57 kD whereas addition of BIM23052 or BIM23056 (sst5 and sst3 sel
ective respectively) does not. This pharmacological profile correspond
s to sst2. (4) Only RNA message of sst2 gene is detected in IGR-N-91 c
ells and its metastases derived sublines by reverse-transcription-poly
merase chain reaction and Northern hybridization in keeping with the p
resence of sst2. (5) In human biopsies, the complex of 57 kD correspon
ding to sst2 is consistently detected in three samples of the histolog
ical subset of the disease: benign ganglioneuroma, ganglioneuroblastom
a and immature neuroblastoma. Therefore, the sst2 should be considered
as the primary target to develop more potent SS analogues for neurobl
astoma therapy or/and scintigraphy.