Granulocyte colony-stimulating factor/granulocyte colony-stimulating factor receptor biological axis promotes survival and growth of baldder cancer cells
Granulocyte colony-stimulating factor/granulocyte colony-stimulating factor receptor biological axis promotes survival and growth of baldder cancer cells
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DOI：
10.1016/j.urology.2007.02.035
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发表时间：
2007-06-01
期刊：
影响因子：
2.1
通讯作者：
Guha, Sushovan
中科院分区：
文献类型：
--
作者：
Chakraborty, Arup;Guha, Sushovan
目的研究粒细胞集落刺激因子（G-CSF）和粒细胞集落刺激因子受体（G-CSFR）在浸润性膀胱癌中的表达。我们试图确定G-CSF/G-CSFR信号传导是否促进膀胱癌细胞的存活和生长。膀胱癌细胞系5637组成性分泌G-CSF，但缺乏G-CSFR表达。相反，TCC-CSF缺乏G-CSF和G-CSFR两者的表达。方法将空载体（3.1）和G-CSFR（GR）分别瞬时转染膀胱癌细胞系TCC-10和5637，观察G-CSFR表达对膀胱癌细胞增殖、存活和生长的影响。MTT法检测G-CSF对TCC-GR-3.1和TCC-GR-3.1细胞增殖的影响。用流式细胞术检测5637-GR中有或没有抗G-CSF抗体的细胞凋亡，以及在G-CSF浓度增加的情况下TCC-GR-GR中的细胞凋亡。我们通过Western blotting检测了STAT 3（signal transducer and activator of transcription 3）显性负表达对G-CSF/G-CSFR介导的STAT 3磷酸化的影响。我们通过流式细胞术在TCC-β-3.1和TCC-β-GR细胞中表征了STAT 3显性阴性表达对G-CSF/G-CSFR介导的survivin表达的影响。结果G-CSF/G-CSFR环能显著促进TCC-GR-GR细胞的增殖。抗G-CSF抗体可显著增加血清饥饿的5637-GR细胞的凋亡，G-CSF可剂量依赖性地抑制血清饥饿的TCC-GR-GR细胞的凋亡。STAT 3显性阴性表达阻断G-CSF介导的STAT 3磷酸化和Survivin在TCC-GR细胞中的表达。结论G-CSF/G-CSFR自分泌/旁分泌信号环能显著促进膀胱癌细胞的存活和生长。
Objectives A significant fraction of invasive bladder carcinomas express both granulocyte colony-stimulating factor (G-CSF) and granulocyte colony-stimulating factor receptor (G-CSFR). We sought to determine whether G-CSF/G-CSFR signaling promotes survival and growth of bladder cancer cells. The bladder carcinoma celt line 5637 constitutively secretes G-CSF but lacks G-CSFR expression. In contrast, TCC-SUP lacks expression of both G-CSF and G-CSFR. Using these bladder cancer cell lines as our model systems, we studied the effects of G-CSFR expression on cell proliferation, survival, and growth in vivo.Methods The TCC-SUP and 5637 cells were transiently transfected with either empty vector (3.1) or G-CSFR (GR). Cell proliferation was assessed with or without G-CSF by MTT assay in TCC-SUP-3.1 and TCC-SUP-GR cells. Apoptosis was examined by flow cytometry in 5637-GR with or without anti-G-CSF antibody and in TCC-SUP-GR in the presence of increasing concentrations of G-CSF. We examined the effects of STAT3 (signal transducer and activator of transcription 3) dominant-negative expression on G-CSF/G-CSFR-mediated STAT3 phosphorylation by Western blotting in TCC-SUP-3.1 and TCC-SUP-GR cells. We characterized the effects of STAT3-dominant-negative expression on G-CSF/G-CSFR-mediated survivin expression by flow cytometry in TCC-SUP-3.1 and TCC-SUP-GR cells. We also examined tumor growth using 5637-3.1 and 5637-GR in the nude mice xenograft model.Results The G-CSF/G-CSFR loop significantly increased proliferation in TCC-SUP-GR cells. Anti-G-CSF antibody significantly increased apoptosis in serum-starved 5637-GR cells, G-CSF abrogated apoptosis in serum-starved TCC-SUP-GR cells in a dose-dependent manner. STAT3-dominant-negative expression blocked G-CSF-mediated STAT3 phosphorylation and survivin expression in TCC-SUP-GR cells. Furthermore, 5637-GR cells produced a significantly larger tumor in the subcutaneous nude mice xenograft model.Conclusions The G-CSF/G-CSFR autocrine/paracrine signaling loop significantly promotes survival and growth of bladder cancer cells.