Evaluation of receptors for somatostatin in various tumors using different analogs

Gordan Srkalovic, Ren Zhi Cai, Andrew V Schally

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The binding characteristics of several somatostatin (SS-14) analogs developed in our laboratory were examined in various human and animal tumors and normal tissues. In rat cerebral cortex and human breast cancer membranes the interaction of SS-14 with its binding sites was rapid, specific, saturable, linear with protein concentrations, and dependent on time and temperature. Analysis of kinetic and equilibrium experimental data showed that the interaction of [125I-Tyr11]SS-14 with the binding sites in all normal and tumoral tissue specimens was consistent with the presence of a single class of noncooperative binding sites. Superactive octapeptide analogs of somato-statin-containing hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys showed significant binding affinities to SS-14 receptors. Among these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I) showed the highest binding affinity to normal human pancreatic tissue and human pancreatic adenocarcinoma. In contrast, Sandostatin (SMS 201-995) bound only to normal pancreas, not to human pancreatic cancers. Analog RC-98-I also showed a high binding to human and rat prostate cancers. In human epithelial ovarian cancers and an arrhenoblastoma, analogs D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2, (RC-95-I), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) appeared to be the most potent in displacing labeled SS-14. Analogs Ac-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-101-I) as well as RC-121, RC-160, and RC-95-I, but not SMS-201-995, showed high binding affinity in human breast cancers. In specimens of human meningioma the highest binding was found with analogs RC-121, RC-95-I, and RC-101-I. Since marked variations in binding affinities were noted for several analogs in the tissues of origin and the tumors, this suggests that differences may exist between somatostatin receptors not only in normal us. cancerous tissues, but also among various tumors. Our findings also imply that some analogs could be therapeutically superior to others in the treatment of certain tumors.

Original languageEnglish
Pages (from-to)661-669
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume70
Issue number3
StatePublished - Dec 1 1990
Externally publishedYes

Fingerprint

Somatostatin Receptors
Tumors
Octreotide
Tissue
Binding Sites
Neoplasms
Rats
Hydroxymethylglutaryl-CoA Reductase Inhibitors
cysteinyltyrosine
Somatostatin
Sertoli-Leydig Cell Tumor
Animals
Breast Neoplasms
Membranes
Kinetics
Meningioma
Pancreatic Neoplasms
Cerebral Cortex
Pancreas
Prostatic Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Evaluation of receptors for somatostatin in various tumors using different analogs. / Srkalovic, Gordan; Cai, Ren Zhi; Schally, Andrew V.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 70, No. 3, 01.12.1990, p. 661-669.

Research output: Contribution to journalArticle

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