Demonstration of multiple phenotypic diversity in a murine melanoma of recent origin.

Demonstration of multiple phenotypic diversity in a murine melanoma of recent origin.
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最近起源的小鼠黑色素瘤的多种表型多样性的证明。

DOI:
10.1093/jnci/67.4.947
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发表时间:
1981
期刊:
Journal of the National Cancer Institute
影响因子:
--
通讯作者:
C. Bucana
C. Bucana
中科院分区:
--
文献类型:
--
作者:
I. J. Fidler;Eilene Gruys;Maria A. Cifone;Zoa L. Barnes;C. Bucana

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这些研究的目的是检查在连续移植肿瘤中经常发现的转移异质性是否可以在最近起源的小鼠黑素瘤中观察到。将在近交系C3 H/HeN小鼠乳腺肿瘤病毒阴性(C3 H-)小鼠中产生的原发性K-1735黑色素瘤一次性移植到免疫抑制受体中,然后在培养物中建立。来自第五次体外传代的细胞用于产生克隆。亲本K-1735和22个克隆系在同系和远交的N:NIH(S)裸鼠中具有致瘤性。通过观察将细胞静脉注射到6周龄C3 H-小鼠中后细胞产生肺和肺外病变的能力来评估转移特性。产生的转移瘤的数量,它们的相对大小和色素沉着在克隆中变化很大。22个克隆中只有2个与母瘤无法区分。大多数非转移性(但致瘤性克隆)在3周龄裸鼠中也是非转移性的,这表明没有转移形成不仅仅是由于它们被正常C3 H-小鼠免疫排斥。对照亚克隆实验表明,体外克隆的程序是不负责的变异性之间的克隆。这些克隆在核型或细胞大小上没有差异,但它们在体外的生长速度确实不同。然而,这些表型与转移倾向无关。总之,K-1735是一种最新来源的小鼠黑色素瘤,具有异质性,包含具有不同生物学行为的细胞亚群。
The purpose of these studies was to examine whether the metastatic heterogeneity that is frequently found in serially transplanted neoplasms could be observed in a murine melanoma of recent origin. The primary K-1735 melanoma that arose in an inbred C3H/HeN murine mammary tumor virus-negative (C3H-) mouse was transplanted once into an immunosuppressed recipient and then established in culture. Cells from the fifth in vitro passage were used to produce clones. The parent K-1735 and 22 cloned lines were tumorigenic in syngeneic and outbred N:NIH(S) nude mice. Metastatic properties were assessed by observing the ability of the cells to produce pulmonary and extrapulmonary lesions after they were injected iv into 6-week-old C3H- mice. The number of metastases produced, their relative size, and pigmentation varied dramatically among the clones. Only 2 of 22 clones were indistinguishable from the parent tumor. Most of the nonmetastatic (but tumorigenic clones) were also nonmetastatic in 3-week-old nude mice, which suggests that the absence of metastasis formation was not merely due to their immunologic rejection by the normal C3H- mouse. Control subcloning experiments demonstrated that the procedure of cloning in vitro was not responsible for the variability among the clones. The clones did not differ in their karyotype or cell size, but they did differ in their growth rate in vitro. These phenotypes, however, did not correlate with metastatic propensity. In conclusion, the K-1735, a murine melanoma of most recent origin, is heterogeneous and contains subpopulations of cells with diverse biologic behavior.