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Oncotarget:CXCR4在乳腺癌和正常细胞中起着不同的作用

  1. CXCR4
  2. 乳腺癌
  3. 乳腺癌干细胞
  4. 正常细胞

来源:生物谷 2014-06-21 17:18

在制定有效的癌症疗法中的一个关键步骤是确定正常,健康细胞和癌细胞之间的差异,这些差异可以被利用来特异性杀伤肿瘤细胞。

2014年6月21日讯 /生物谷BIOON/--在制定有效的癌症疗法中的一个关键步骤是确定正常,健康细胞和癌细胞之间的差异,这些差异可以被利用来特异性杀伤肿瘤细胞。

曼彻斯特科学家一项新的研究第一次对比了一种特定的蛋白质CXCR4在正常和癌变乳腺干细胞中的影响,了解CXCR4对上述细胞的差异性意味着它可以被利用来开发乳腺癌更有针对性的治疗。CXCR4已经在23个不同类型的癌症中被发现,并已与癌症预后较差相关。

现在,研究人员研究CXCR4在正常乳腺干细胞和癌变乳腺干细胞的作用。曼彻斯特大学-曼彻斯特癌症研究中心科研小组发现,该蛋白控制乳腺癌干细胞的增殖,在癌症扩散中发挥潜在作用。

研究领导者Rob Clarke博士说:我们知道,CXCR4调控肺癌,胰腺癌和前列腺癌中的癌症干细胞生长,CXCR4也与乳腺癌不良预后有关,我们希望能够更好地理解CXCR4在乳腺干细胞中扮演的角色。

这项发表在Oncotarget杂志上的新研究表明CXCR4在乳腺干细胞中水平提高。然而,只有在乳腺癌中,CXCR4才控制乳腺癌干细胞的生长。Clarke博士补充说:这种分子在健康和癌组织中的不同作用可能是非常有趣的,可以用来专门针对癌症干细胞,但我们仍然需要更多地了解这些观察到的差异的根本机制。(生物谷Bioon.com)

 

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A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity

Ablett et al.

C-X-C chemokine receptor type 4 (CXCR4) is known to regulate lung, pancreatic and prostate cancer stem cells. In breast cancer, CXCR4 signalling has been reported to be a mediator of metastasis, and is linked to poor prognosis. However its role in normal and malignant breast stem cell function has not been investigated. Anoikis resistant (AR) cells were collected from immortalised (MCF10A, 226L) and malignant (MCF7, T47D, SKBR3) breast cell lines and assessed for stem cell enrichment versus unsorted cells. AR cells had significantly higher mammosphere forming efficiency (MFE) than unsorted cells. The AR normal cells demonstrated increased formation of 3D structures in Matrigel compared to unsorted cells. In vivo, SKBR3 and T47D AR cells had 7- and 130-fold enrichments for tumour formationrespectively, compared with unsorted cells. AR cells contained significantly elevated CXCR4 transcript and protein levels compared to unsorted cells. Importantly, CXCR4 mRNA was higher in stem cell-enriched CD44+/CD24- patient-derived breast cancer cells compared to non-enriched cells. CXCR4 stimulation by its ligand SDF-1 reduced MFE of the normal breast cells lines but increased the MFE in T47D and patient-derived breast cancer cells. CXCR4 inhibition by AMD3100 increased stem cell activity but reduced the self-renewal capacity of the malignant breast cell line T47D. CXCR4+ FACS sorted MCF7 cells demonstrated a significantly increased MFE compared with CXCR4- cells. This significant increase in MFE was further demonstrated in CXCR4 over-expressing MCF7 cells which also had an increase in self-renewal compared to parental cells. A greater reduction in self-renewal following CXCR4 inhibition in the CXCR4 over-expressing cells compared with parental cells was also observed. Our data establish for the first time that CXCR4 signalling has contrasting effects on normal and malignant breast stem cell activity. Here, we demonstrate that CXCR4 signalling specifically regulates breast cancer stem cell activities and may therefore be important in tumour formation at the sites of metastases.

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