Octreotide and pasireotide (dis)similarly inhibit pituitary tumor cells in vitro

Abstract

Somatostatin analogs (SSA) are the mainstay of pharmacological treatment for pituitary adenomas. However, some patients escape from therapy with octreotide, a somatostatin receptor 2 (sst2)-preferring SSA, and pasireotide, a novel multi-sst-preferring SSA, may help to overcome this problem. It has been proposed that correspondence between sst1-sst5 expression pattern and SSA-binding profile could predict patient's response. To explore the cellular/molecular features associated with octreotide/pasireotide response, we performed a parallel comparison of their in vitro effects, evaluating sst1-sst5 expression, intracellular Ca signaling ([Ca]), hormone secretion and cell viability, in a series of 85 pituitary samples. Somatotropinomas expressed sst5>sst2, yet octreotide reduced [Ca] more efficiently than pasireotide, while both SSA similarly decreased growth hormone release/expression and viability. Corticotropinomas predominantly expressed sst5, but displayed limited response to pasireotide, while octreotide reduced functional endpoints. Non-functioning adenomas preferentially expressed sst3 but, surprisingly, both SSA increased cell viability. Prolactinomas mainly expressed sst1 but were virtually unresponsive to SSA. Finally, both SSA decreased [Ca] in normal pituitaries. In conclusion, both SSA act in vitro on pituitary adenomas exerting both similar and distinct effects; however, no evident correspondence was found with the sst1-sst5 profile. Thus, it seems plausible that additional factors, besides the simple abundance of a given sst, critically influence the SSA response.

Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target

“…Analogous findings of decreased cell viability have been shown with the use of octreotide and pasireotide in various types of pituitary tumors, regardless of SSTR subtype expression pattern, in vitro 39. The findings of the present study suggest this may be mediated by SSTR-induced upregulation of the direct pro-apoptotic factor BAX.…”

Association between dopamine and somatostatin receptor expression and pharmacological response to somatostatin analogues in acromegaly

“…No patient received radiotherapy before surgery. Of the 74 patients, we were able to obtain reliable biochemical data to evaluate response to SSAs treatment from 58 patients either before surgery (30) or adjuvant (28). Missing data were due to incomplete follow-up.…”

Somatostatin receptor subtype 1 as a potential diagnostic marker and therapeutic target in prostate cancer

“…Some components of this system have been previously associated with development and progression of tumoral pathologies, such as pituitary adenomas, thyroid cancer, neuroendocrine tumors (NETs), and breast cancer, where they may exert an important role as diagnosis/prognosis markers and therapeutic targets . In fact, somatostatin analogs (eg, the sst2‐preferring octreotide and lanreotide, and the pan‐sst ligand pasireotide) are currently being used to treat some of these pathologies, such as pituitary adenomas and NETs, highlighting the clinical relevance of this system …”

“…[22][23][24] In fact, somatostatin analogs (eg, the sst2-preferring octreotide and lanreotide, and the pan-sst ligand pasireotide) are currently being used to treat some of these pathologies, such as pituitary adenomas and NETs, highlighting the clinical relevance of this system. [25][26][27] It has been demonstrated that the expression of some components of the SST system, especially sst variants, are dysregulated in PCa tissue and associated with the aggressiveness of tumor cells, [28][29][30] which highlights the putative utility of these components as novel biomarkers and therapeutic targets to develop pharmacologic strategies for this pathology. In this sense, SST receptor subtype 1 (sst1, SSTR1) has been described as an important molecule in several types of cancer, such as colon cancer, where it seems to play a significant role and is associated with some aggressiveness features.…”