Antineoplastic and Antiangiogenic Actions of Somatostatin Analogs
Somatostatin is a tetradecapeptide which participates in a variety of biological processes, including inhibition of exocrine and hormonal secretions and cell proliferation (Lamberts, 1991; Pollak and Serially, 1998). These properties are used for the treatment of hormone-producing pituitary or gastroen-teropancreatic tumors by stable somatostatin analogs. Thus, hormonal suppression is produced in patients with acromegaly, or with neuroendocrine tumors such as insulinoma, glucagonoma, gastrinoma, vipoma or carcinoid syndrome. In some patients analog therapy leads to an inhibition of tumor growth. Somatostatin exerts an antiproliferative effect, either by indirectly inhibiting hormone and growth factor release, or by an inhibition of angio-genesis, or by acting directly on neoplastic cells. Somatostatin exerts its biological effects by interacting with specific receptors, which have been detected by binding assay or autoradiography in various human tumors and normal tissues. These proteins are expressed in a tissue-specific manner. A total of five somatostatin receptor subtypes (sst1–sst5) and one splice variant have been cloned from human, mouse and rat (Bell and Reisine, 1993; Hoyer et al., 1995). After expression of sst1–sst5 gene clones in mammalian cell lines we and others demonstrated a distinct profile for binding of clinically employed somatostatin analogs, such as SMS 201–995 (octreotide), BIM 23014 (lan-reotide) and RC-160 (vapreotide).
KeywordsPancreatic Carcinoma Human Pancreatic Cancer Cell Growth Factor Release Octreotide Acetate Pancreatic Cancer Model
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