High expression of somatostatin receptor subtype 2 (sst2) in medulloblastoma: implications for diagnosis and therapy.
Medulloblastoma is a pediatric malignancy, which arises in cerebellum. The neuropeptide somatostatin (SS-14) is a neuromodulator and growth regulator in the developing cerebellum. SS-14 has previously been demonstrated in medulloblastomas with immunohistochemical techniques, but somatostatin receptor (sst) expression is less well understood. We analyzed somatostatin and sst subtype expression (sst1-5) in central primitive neuroectodermal tumors (cPNET), including 23 medulloblastomas, 6 supratentorial PNET, and 10 cPNET cell lines. The expression of SS-14 and sst genes in cPNET was compared with expression of these genes in 17 tumors of the Ewing's sarcoma family of tumors using reverse transcriptase-PCR, Southern hybridization, quantitative in vitro receptor autoradiography, and competitive membrane binding assays. The sst1 subtype was expressed in similar frequency in cPNET (83%) and Ewing's sarcoma family of tumors (71%). Nine of the 10 cell lines and 76% of the cPNET expressed mRNA for sst2 compared with 35% of the Ewing's sarcoma family of tumors. High-affinity binding of SS-14 was demonstrated in cPNET by quantitative autoradiography as well as by competitive binding assays. The cPNET cell line D283 Med bound SS-14 and octreotide with high affinity; SS-14 inhibited proliferation of D283 Med cells as measured by a decrease in [3H]thymidine uptake. We conclude that both sst1 and sst2 are highly expressed in cPNET and suggest that somatostatin may regulate proliferation and differentiation in these developmental tumors.
Frühwald
M C
MC
Department of Pediatrics, Ohio State University, Columbus 43205, USA.
O'Dorisio
M S
MS
Pietsch
T
T
Reubi
J C
JC
D000293:Adolescent; D000328:Adult; D002528:Cerebellar Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D017481:Receptors, Somatostatin / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2