A new tumorsphere culture condition restores potentials of self-renewal and metastasis of primary neuroblastoma in a mouse neuroblastoma model.
A new tumorsphere culture condition restores potentials of self-renewal and metastasis of primary neuroblastoma in a mouse neuroblastoma model.
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DOI：
10.1371/journal.pone.0086813
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kadomatsu K
中科院分区：
文献类型：
--
作者：
Cao D;Kishida S;Huang P;Mu P;Tsubota S;Mizuno M;Kadomatsu K
肿瘤球培养可以富集和扩增肿瘤细胞，从而为癌症研究提供重要资源。然而，与转移性组织相比，神经系统原发性肿瘤很少产生长期存活的肿瘤球，从而严重限制了对这些癌症的研究。这可能是由于肿瘤细胞的自我更新能力有限和/或培养条件不合适。肿瘤细胞的生长和维持可取决于微环境和/或细胞起源（例如，原发性或转移性;干细胞样或祖细胞样）。在这里，我们试图建立一个肿瘤球培养条件的原发性神经母细胞瘤（NB）。MYCN转基因小鼠（NB模型）中的原发性肿瘤可以连续移植，这表明这些肿瘤含有具有高自我更新潜力的细胞。然而，原发性肿瘤在无血清神经球培养条件下不会产生肿瘤球。新建立的培养条件（命名为PrimNeuS）包含两个关键成分：胎牛血清和β-巯基乙醇是肿瘤球形成以及无限传代所必需的。在此条件下，该球可传代20次以上而不衰竭，表现出分化的性质，并在体内形成肿瘤。出乎意料的是，PrimNeuS发现MYCN转基因小鼠有骨髓转移。此外，原发肿瘤的肿瘤球衍生的皮下肿瘤显示骨髓转移。综上所述，PrimNeuS为NB的研究提供了资源，并可用作检测微小残留病变和个性化治疗前体外评价的有力工具。
Tumorsphere culture enriches and expands tumor cells, thus providing important resources for cancer studies. However, as compared with metastatic tissues, primary tumors in the nervous system rarely give rise to long-surviving tumorspheres, thereby seriously limiting studies on these cancers. This might be due to the limited self-renewal capability of tumor cells and/or to inappropriate culture conditions. The growth and maintenance of tumor cells may depend on microenvironments and/or cell origins (e.g., primary or metastatic; stem cell-like or progenitor-like). Here, we attempted to establish a tumorsphere culture condition for primary neuroblastoma (NB). Primary tumors in MYCN transgenic mice, a NB model, could be serially transplanted, suggesting that these tumors contain cells with a high self-renewal potential. However, primary tumors did not give rise to tumorspheres under a serum-free neurosphere culture condition. The newly established culture condition (named PrimNeuS) contained two critical ingredients: fetal bovine serum and β-mercaptoethanol were essential for tumorsphere formation as well as indefinite passages. The spheres could be passaged more than 20 times without exhaustion under this condition, exhibited a property of differentiation and formed tumors in vivo. Unexpectedly, PrimNeuS revealed that the MYCN transgenic mice had bone marrow metastasis. Furthermore, subcutaneous tumors derived from tumorspheres of primary tumors showed bone marrow metastasis. Taken together, PrimNeuS provides resources for the study of NB and can be used as a powerful tool for the detection of minimal residual disease and for in vitro evaluation prior to personalized therapy.
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影响因子：
64.5
作者：
Roesch A;Fukunaga-Kalabis M;Schmidt EC;Zabierowski SE;Brafford PA;Vultur A;Basu D;Gimotty P;Vogt T;Herlyn M
通讯作者：
Herlyn M
影响因子：
64.5
作者：
Hanna JH;Saha K;Jaenisch R
通讯作者：
Jaenisch R
影响因子：
9.7
作者：
Nakagawara, A;Ohira, M
通讯作者：
Ohira, M
影响因子：
50.3
作者：
Chen, Ruihuan;Nishimura, Merry C.;Phillips, Heidi S.
通讯作者：
Phillips, Heidi S.
影响因子：
64.5
作者：
Ang YS;Tsai SY;Lee DF;Monk J;Su J;Ratnakumar K;Ding J;Ge Y;Darr H;Chang B;Wang J;Rendl M;Bernstein E;Schaniel C;Lemischka IR
通讯作者：
Lemischka IR