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识别人类脑肿瘤起始细胞

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识别人类脑肿瘤起始细胞

肿瘤干细胞(CSC)假说认为新生肿瘤的复制是由一部分罕见的,具有干细胞功能的细胞专门来维持的。尽管在白血病中存在这种肿瘤干细胞(CSC)是被确定的,但确很少有证据表面这种肿瘤干细胞(CSC)存在于实体瘤中,乳腺癌除外。最近,我们在期盼中从人类的脑肿瘤中分离到了一个CD133+的细胞亚群,其在体外表现为干细胞功能。然而,肿瘤干细胞(CSC)的真正检测(http://www.chemdrug.com/sell/76/)手段是其自我修复及其对原位癌的准确重现的能力。这里我们报道一种肿瘤异种移植物检测的形成,这种方法用于识别人脑肿瘤起始细胞。在那些非肥胖性糖尿病和重症联合免疫缺陷(NOD-SCID)的小鼠颅内,仅有CD133阳性的脑肿瘤的部位包含了那些具有起始肿瘤的细胞。灌注100个左右CD133阳性细胞能长生一种能连续移植并具有病人初始肿瘤表型的一种肿瘤。而灌注105 CD133阴性的细胞并不能引起肿瘤。因此,对于脑肿瘤起始细胞的鉴定提供了对人脑肿瘤发病机制研究的新观点,对CSC假说做为许多实体瘤的基础的有力支持,并建立了一种先前未确定的能用于肿瘤治疗的靶细胞。

Identification of human brain tumour initiating cells

The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell properties. Although the existence of CSCs in human leukaemia is established, little evidence exists for CSCs in solid tumours, except for breast cancer. Recently, we prospectively isolated a CD133+ cell subpopulation from human brain tumours that exhibited stem cell properties in vitro. However, the true measures of CSCs are their capacity for self renewal and exact recapitulation of the original tumour. Here we report the development of a xenograft assay that identified human brain tumour initiating cells that initiate tumours in vivo. Only the CD133+ brain tumour fraction contains cells that are capable of tumour initiation in NOD-SCID (non-obese diabetic, severe combined immunodeficient) mouse brains. Injection of as few as 100 CD133+ cells produced a tumour that could be serially transplanted and was a phenocopy of the patient's original tumour, whereas injection of 105 CD133- cells engrafted but did not cause a tumour. Thus, the identification of brain tumour initiating cells provides insights into human brain tumour pathogenesis, giving strong support for the CSC hypothesis as the basis for many solid tumours, and establishes a previously unidentified cellular target for more effective cancer therapies.

Nature 432, 396 - 401 (18 November 2004); doi:10.1038/nature03128

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v432/n7015/abs/nature03128_fs.html&dynoptions=doi1101481265

 
 
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