Effects of pasireotide on bronchial carcinoids in primary culture

Bronchopulmonary endocrine tumors represent 25–30% of lung neoplasms. Surgery provides good survival for differentiated tumors (typical and atypical carcinoids), but is not useful for aggressive poorly differentiated forms. Somatostatin (SRIF) analogs can be used as medical therapy, prolonging patient survival. However, the compounds employed so far did not display antiproliferative effects. Recently, a new stable SRIF analog, pasireotide (SOM230), which activates SSTR1, 2, 3, and 5, has been developed. Our study aimed at clarifying whether SOM230 might affect cell viability of bronchial carcinoids in vitro. We assessed SRIF receptor expression pattern, both at mRNA and protein level, as well as the in vitro effects of SOM230 on cell viability. Sixteen brochial carcinoids (13 typical and 3 atypical carcinoids) were examined by RT-PCR and by microscopy immunofluorescence for expression of Chromogranin A (CgA) and SSTRs. In addition, primary cultures were tested with SOM230 in vitro. All samples expressed CgA, while SSTR1 was expressed in 14 samples, SSTR2 and SSTR4 in 12, SSTR3 in 5, and SSTR5 in 7 samples. Treatment with SOM230 did not significantly modify cell viability, but was capable of blocking the proliferative effects of Forskolin, a potent stimulator of cyclic AMP (cAMP) pathway. This effect was apparent in primary cultures from carcinoid tumors expressing SSTR1 or SSTR2, as well as in tumors not expressing SSTR3 or SSTR5. Our data demonstrate that cAMP pathway activation up-regulates bronchial carcinoid cell proliferation, which can be inhibited by SOM230 in selected cases. Indeed, our data suggest that this effect is mediated by SSTR1 or SSTR2, and not by SSTR3 or SSTR5. Since SSTR1 and 2 are the most represented among bronchial carcinoids, our data support a possible role for SOM230 as a new tool for medical therapy of these tumors.