EXPRESSION AND LOCALIZATION OF SOMATOSTATIN RECEPTOR SSTR1, SSTR2, AND SSTR3 MESSENGER-RNAS IN PRIMARY HUMAN TUMORS USING IN-SITU HYBRIDIZATION

Somatostatin receptor gene expression of SSTR1, SSTR2, and SSTR3 subty pes was evaluated by in situ hybridization in 55 human primary tumors shown to contain a high density of somatostatin receptors in binding a ssays. Ah 55 tumors expressed at least one SSTR subtype. Of 55 somatos tatin receptor positive tumors, 46 had SSTR2 mRNA; all 46 were charact erized as having receptors with a high affinity for the synthetic anal ogue octreotide. Of 55 tumors, 12 expressed SSTR1, and 14 expressed SS TR3 mRNA. The subtype SSTR1 was expressed alone in 4 cases, SSTR2 was expressed alone in 33 cases, and SSTR3 was expressed alone in one case . In 4 cases, all 3 SSTR were expressed simultaneously. The cases havi ng SSTR1 mRNA were identified in binding experiments with I-125-labele d somatostatin-14 and -28 analogues rather than with I-125-[Tyr(3)]-oc treotide. Whereas meningiomas, neuroblastomas, pituitary adenomas, sma ll cell lung carcinomas, lymphomas, and breast tumors expressed primar ily a high abundance of SSTR2, carcinoids, islet cell carcinomas, medu llary thyroid carcinomas, and ovarian tumors had a mixed distribution of the somatostatin receptor subtypes. This is the first demonstration of the presence of SSTR1, SSTR2, and SSTR3 in primary human tumors us ing in situ hybridization. Since these somatostatin receptor subtypes probably mediate distinct somatostatin actions, it may be worthwhile t o search for subtype-specific analogues to use for the treatment and d iagnosis of these tumors.