Department of Internal Medicine, Life Sciences Institute, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA.
Cancer Cell. 2012 Feb 14;21(2):240-52. doi: 10.1016/j.ccr.2011.12.027.
Tumor-initiating cells have been suggested to be rare in many cancers. We tested this in mouse malignant peripheral nerve sheath tumors (MPNSTs) and found that 18% of primary and 49% of passaged MPNST cells from Nf1(+/-); Ink4a/Arf(-/-) mice formed tumors upon transplantation, whereas only 1.8% to 2.6% of MPNST cells from Nf1(+/-); p53(+/-) mice did. MPNST cells of both genotypes require laminin binding to β1-integrin for clonogenic growth. Most MPNST cells from Nf1(+/-); Ink4a/Arf(-/-) mice expressed laminin, whereas most MPNST cells from Nf1(+/-); p53(+/-) mice did not. Exogenous laminin increased the percentage of MPNST cells from Nf1(+/-); p53(+/-) but not Nf1(+/-); Ink4a/Arf(-/-) mice that formed tumorigenic colonies. Tumor-forming potential is common among MPNST cells, but the assay conditions required to detect it vary with tumor genotype.
肿瘤起始细胞被认为在许多癌症中很少见。我们在鼠恶性外周神经鞘瘤(MPNST)中对此进行了测试,发现 Nf1(+/-); Ink4a/Arf(-/-) 小鼠的原发和传代 MPNST 细胞中有 18%形成肿瘤,而 Nf1(+/-); p53(+/-) 小鼠的 MPNST 细胞中仅有 1.8%至 2.6%形成肿瘤。两种基因型的 MPNST 细胞都需要层粘连蛋白与β1-整合素结合才能进行集落形成生长。Nf1(+/-); Ink4a/Arf(-/-) 小鼠来源的大多数 MPNST 细胞表达层粘连蛋白,而 Nf1(+/-); p53(+/-) 小鼠来源的大多数 MPNST 细胞不表达层粘连蛋白。外源性层粘连蛋白增加了 Nf1(+/-); p53(+/-) 但不增加 Nf1(+/-); Ink4a/Arf(-/-) 小鼠形成致瘤集落的 MPNST 细胞的比例。MPNST 细胞中存在肿瘤形成潜能,但检测它所需的实验条件因肿瘤基因型而异。