Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells

Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells
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DOI:
10.1038/sj.bjc.6690789
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发表时间:
1999-11-01
影响因子:
8.8
通讯作者:
Wheeler, KT
Wheeler, KT
中科院分区:
医学1区
文献类型:
--
作者:
Al-Nabulsi, I;Mach, RH;Wheeler, KT

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最近,我们证明σ-2受体可能具有成为肿瘤细胞增殖的生物标志物的潜力(Mach等(1997)Cancer Res 57:156-161)。如果σ-2受体是肿瘤细胞增殖的生物标志物,则它们将适合于通过非侵入性成像程序进行检测,从而消除与目前临床中使用的肿瘤细胞增殖的流式细胞术测量相关的许多问题。为了成为肿瘤细胞增殖的良好生物标志物,σ-2受体的表达必须基本上独立于实体瘤中发现的许多生物学、生理学和/或环境特性。在本文报道的研究中,小鼠乳腺癌细胞系66(二倍体)和67(二倍体)(非整倍体)、9 L大鼠脑肿瘤细胞和MCF-7人乳腺肿瘤细胞用于研究增殖(P)和静止(Q)肿瘤细胞中σ-2受体表达的程度和动力学,作为物种、细胞类型、倍性、pH、营养物消耗、代谢状态、从Q细胞区室募集到P细胞区室,以及用他莫昔芬治疗。在这些实验中,sigma-2!受体仅反映肿瘤细胞的增殖状态。所研究的生物学、生理学或环境特性中没有一个对这些模型系统中的σ-2受体的表达具有可测量的影响。因此,这些数据表明,肿瘤和正常组织的增殖状态可以使用选择性结合σ-2受体的放射性标记配体进行非侵入性评估。(C)1999年癌症研究。
Recently, we demonstrated that sigma-2 receptors may have the potential to be a biomarker of tumour cell proliferation (Mach et al (1997) Cancer Res 57: 156-161). If sigma-2 receptors were a biomarker of tumour cell proliferation, they would be amenable to detection by non-invasive imaging procedures, thus eliminating many of the problems associated with the flow cytometric measures of tumour cell proliferation presently used in the clinic. To be a good biomarker of tumour cell proliferation, the expression of sigma-2 receptors must be essentially independent of many of the biological, physiological, and/or environmental properties that are found in solid tumours. In the investigation reported here, the mouse mammary adenocarcinoma lines, 66 (diploid) and 67 (aneuploid), 9L rat brain tumour cells, and MCF-7 human breast tumour cells were used to study the extent and kinetics of expression of sigma-2 receptors in proliferative (P) and quiescent (Q) tumour cells as a function of species, cell type, ploidy, pH, nutrient depletion, metabolic state, recruitment from the Q-cell compartment to the P-cell compartment, and treatment with tamoxifen. in these experiments, the expression of sigma-2! receptors solely reflected the proliferative status of the tumour cells. None of the biological, physiological, or environmental properties that were investigated had a measurable effect on the expression of sigma-2 receptors in these model systems. Consequently, these data suggest that the proliferative status of tumours and normal tissues can be non-invasively assessed using radiolabelled ligands that selectively bind sigma-2 receptors. (C) 1999 Cancer Research.