生物谷报道:研究人员发现,通过引入指导炎症细胞和肿瘤细胞迁移的因子,原发肿瘤让肺部作好准备,迎接外来者的入侵,他们将这一最新的研究成果发表在今年12月号的《自然—细胞生物学》上。
许多固体肿瘤是在迁移过程中形成,这时癌细胞从原发位置扩散到身体的其他部位。迁移减少了治疗的机会和晚期癌症出现症状的时间,但对这一过程的研究还处于婴儿时期。
Sachie Hiratsuka 和同事对患肿瘤的小鼠进行了研究,发现在由原发肿瘤分泌的一系列因子的作用下,名为趋化因子的蛋白质被引入肺部。趋化因子诱导炎症细胞和肿瘤细胞迁移到肺部。原发肿瘤和迁移前组织间的圆圈扩大,促进了迁移肿瘤的侵入。中断原发肿瘤和肺部细胞间的圆环信号可有效地阻止小鼠肺部肿瘤的转移。
在早期中断肿瘤细胞向转移点的迁移是一种有效的临床治疗方法,可阻止癌细胞的扩散。
Figure 1. Upregulation of the expression of S100A8 and S100A9 in premetastatic lungs responding to distant primary tumours.
(a) The experimental metastatic model. The premetastatic phase is considered the period of tumour growth at the primary site and the metastatic phase is the period after the intravenous injection of tumour cells into a tumour-bearing mouse. (b) Western blot analysis of S100A8 and S100A9 in premetastatic lungs derived from normal or tumour (+LLC or +B16)-bearing mice 10 or 14 days after the injection of tumour cells into the back. The intensity of the band (quantified using NIH Image software) was normalized to actin and the values are shown beneath each panel. (c) RT–PCR analysis of S100A8 and S100A9 in lung endothelial cells (EC) and Mac 1+-myeloid cells (M) sorted using anti-VEGFR2 and anti-Mac 1 antibodies, respectively, and in the rest of the cells (through). The intensity of the band was normalized to -actin and is shown beneath each panel. (d) The number of Mac 1+-myeloid cells in premetastatic lungs derived from normal, LLC-bearing and B16-bearing mice. Cells were counted in ten tissue sections per lung. The asterisk indicates P <0.05 and the error bars represent s.d. (e) Immunohistochemistry of lung tissues from normal or LLC-bearing mice using anti-S100A8 (A8), anti-VE–cadherin (VE) or anti-Mac1 antibodies. VE–cadherin (FITC), Mac 1 (rhodamine) and S100A8 (FITC or rhodamine) signals were detected by a fluorescence microscopy. Normal rat IgG and rabbit IgG were used for the control. The scale bars represent 50 m.
原文出处:
Nature Cell Biology December 2006, Volume 8 No 12
Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis pp1369 - 1375
Sachie Hiratsuka, Akira Watanabe, Hiroyuki Aburatani & Yoshiro Maru
Published online: 26 November 2006 | doi:10.1038/ncb1507
Abstract | Full text | PDF (2,568K) | Supplementary Information
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