Degrassi A, Hilbert D M, Rudikoff S, Anderson A O, Potter M, Coon H G
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2060-4. doi: 10.1073/pnas.90.5.2060.
Attempts to grow primary murine plasmacytomas in vitro have, to date, been largely unsuccessful. In this study, we demonstrate that long-term in vitro growth of primary plasmacytomas is accomplished by using feeder layers composed of stromal cells from the initial site of plasmacytomagenesis. The early neoplastic lines established in this manner are dependent on physical contact with the stromal layer, which is mediated in part by CD44, for growth and survival. The stromal cells provide at least two stimuli for the plasma cells, one being interleukin 6 and the second, of unknown nature, resulting from direct physical interaction that cannot be replaced by soluble factors. These plasma cell lines have been passaged for as long as 20 months yet still maintain characteristics associated with primary plasmacytomas as they will grow in vivo only in pristane-primed animals, indicating a continued dependence on the pristane-induced microenvironment characteristic of early-stage tumors. The ability to grow primary plasmacytomas in culture and maintain their "primary" properties provides a model system for detailed analysis of early events in plasma cell tumor progression involving neoplastic cells completely dependent on physical contact with a stromal feeder layer for survival and expansion.
迄今为止,在体外培养原发性小鼠浆细胞瘤的尝试大多未成功。在本研究中,我们证明,通过使用由浆细胞瘤发生初始部位的基质细胞组成的饲养层,可以实现原发性浆细胞瘤的长期体外生长。以这种方式建立的早期肿瘤细胞系的生长和存活依赖于与基质层的物理接触,这部分是由CD44介导的。基质细胞为浆细胞提供至少两种刺激,一种是白细胞介素6,另一种性质不明,是由直接物理相互作用产生的,不能被可溶性因子替代。这些浆细胞系已经传代长达20个月,但仍然保持与原发性浆细胞瘤相关的特征,因为它们仅在经 pristane 预处理的动物体内生长,这表明它们持续依赖于早期肿瘤特有的 pristane 诱导的微环境。在培养中生长原发性浆细胞瘤并维持其“原发性”特性的能力,为详细分析浆细胞肿瘤进展早期事件提供了一个模型系统,这些早期事件涉及肿瘤细胞完全依赖与基质饲养层的物理接触来生存和扩增。