Insulin-like growth factor I is a dual effector of multiple myeloma cell growth.
Insulin-like growth factor I is a dual effector of multiple myeloma cell growth.
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DOI：
10.1182/blood.v96.8.2856.h8002856_2856_2861
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发表时间：
2000-10
期刊：
影响因子：
20.3
通讯作者：
N. Ge;S. Rudikoff
中科院分区：
文献类型：
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作者：
N. Ge;S. Rudikoff
多发性骨髓瘤（MM）是一种不可避免的致命疾病，约占所有人类癌症的1%至2%。令人惊讶的是，我们对促进这些肿瘤生长的细胞途径知之甚少。虽然细胞因子白介素-6已被认为是骨髓瘤细胞生长的主要刺激因素，但第二种潜在生长因子，胰岛素样生长因子I （IGF-I）的作用尚未明确定义。在8 MM细胞系中检测了IGF-I信号级联。在其中7例中，IGF-I受体（IGF-IR）在配体的作用下表达并自磷酸化。在IGF-IR的下游，胰岛素受体底物1被磷酸化，导致磷脂酰肌醇-3'-激酶（PI-3K）的激活。PI-3K反过来调节2种不同的途径。前者包括Akt和Bad，导致细胞凋亡受到抑制；第二种包括丝裂原活化蛋白激酶（MAPK），导致细胞增殖。这一途径的生物学相关性已被证明，因为在体外，IGF-I诱导了抗凋亡和增殖作用。重要的是，在接种了OPM-2细胞系的SCID小鼠体内给药IGF-I导致肿瘤细胞的生长速度大约是对照组的两倍。这些结果表明，igf - 1激活了至少2条影响骨髓瘤细胞生长的途径，并显著促进了骨髓瘤细胞在体内的增殖。(血。2000;96:2856 - 2861)
Multiple myeloma (MM) is an invariably fatal disease that accounts for approximately 1% to 2% of all human cancers. Surprisingly little is known about the cellular pathways contributing to growth of these tumors. Although the cytokine interleukin-6 has been suggested to be the major stimulus for myeloma cell growth, the role of a second potential growth factor, insulin-like growth factor I (IGF-I), has been less clearly defined. The IGF-I signaling cascade in 8 MM cell lines was examined. In 7 of these, the IGF-I receptor (IGF-IR) was expressed and autophosphorylated in response to ligand. Downstream of IGF-IR, insulin receptor substrate 1 was phosphorylated, leading to the activation of phosphatidylinositol-3'-kinase (PI-3K). PI-3K, in turn, regulated 2 distinct pathways. The first included Akt and Bad, leading to an inhibition of apoptosis; the second included the mitogen-activated protein kinase (MAPK), resulting in proliferation. Biologic relevance of this pathway was demonstrated because in vitro IGF-I induced both an antiapoptotic and a proliferative effect. Importantly, in vivo administration of IGF-I in SCID mice inoculated with the OPM-2 line led to approximately twice the growth rate of tumor cells as in controls. These results suggest that IGF-I activates at least 2 pathways effecting myeloma cell growth and contributes significantly to expansion of these cells in vivo. (Blood. 2000;96:2856-2861)