Georgii-Hemming P, Strömberg T, Janson E T, Stridsberg M, Wiklund H J, Nilsson K
Department of Genetics and Pathology and Department of Medical Sciences, University Hospital, Uppsala, Sweden.
Blood. 1999 Mar 1;93(5):1724-31.
Somatostatin and its analogs can inhibit growth in several cell types, in part by interfering with insulin-like growth factor-I (IGF-I) signaling. Our previous studies point to the importance of paracrine and autocrine IGF-I in the support of growth and survival of human multiple myeloma (MM) cell lines. In this report, we have investigated the potential role of a somatostatin analog, octreotide, in regulating growth and/or survival in MM. The results show that all MM cell lines express functional somatostatin receptors (sst). The MM cell lines express the subtypes sst2, sst3, and predominantly sst5 as determined by reverse-transcriptase polymerase chain reaction and fluorescence-activated cell sorter analysis. Octreotide inhibited the growth of both the interleukin-6 (IL-6)-dependent and the IL-6-independent MM cell lines. The effect is mainly cytostatic, resulting in 25% to 45% growth inhibition, and in three of eight of the MM cell lines a weak induction of apoptosis was recorded. Our results also show that octreotide may act as an inducer of apoptosis in primary B-B4(+) plasma cells isolated from bone marrow of MM patients. In conclusion, the results show a novel pathway for growth inhibition of MM cells: the activation of somatostatin receptor signaling.
生长抑素及其类似物可抑制多种细胞类型的生长,部分是通过干扰胰岛素样生长因子-I(IGF-I)信号传导来实现的。我们之前的研究指出,旁分泌和自分泌的IGF-I在支持人多发性骨髓瘤(MM)细胞系的生长和存活方面具有重要作用。在本报告中,我们研究了生长抑素类似物奥曲肽在调节MM生长和/或存活中的潜在作用。结果显示,所有MM细胞系均表达功能性生长抑素受体(sst)。通过逆转录聚合酶链反应和荧光激活细胞分选分析确定,MM细胞系表达sst2、sst3亚型,且主要表达sst5亚型。奥曲肽抑制了白细胞介素-6(IL-6)依赖性和IL-6非依赖性MM细胞系的生长。其作用主要是细胞生长停滞,导致生长抑制25%至45%,并且在八个MM细胞系中有三个记录到微弱的凋亡诱导现象。我们的结果还表明,奥曲肽可能作为从MM患者骨髓中分离出的原代B-B4(+)浆细胞凋亡的诱导剂。总之,结果显示了MM细胞生长抑制的一条新途径:生长抑素受体信号的激活。