Haynes-Gimore Nikesha, Banach Maureen, Brown Edward, Dawes Ryan, Edholm Eva-Stina, Kim Minsoo, Robert Jacques
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Pathology, University of Rochester Medical Center, Rochester, USA.
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Dev Biol. 2015 Dec 15;408(2):205-12. doi: 10.1016/j.ydbio.2015.01.003. Epub 2015 Jan 17.
Tumors have the ability to grow as a self-sustaining entity within the body. This autonomy is in part accomplished by the tumor cells ability to induce the formation of new blood vessels (angiogenesis) and by controlling cell trafficking inside the tumor mass. These abilities greatly reduce the efficacy of many cancer therapies and pose challenges for the development of more effective cancer treatments. Hence, there is a need for animal models suitable for direct microscopy observation of blood vessel formation and cell trafficking, especially during early stages of tumor establishment. Here, we have developed a reliable and cost effective tumor model system in tadpoles of the amphibian Xenopus laevis. Tadpoles are ideally suited for direct microscopy observation because of their small size and transparency. Using the thymic lymphoid tumor line 15/0 derived from, and transplantable into, the X. laevis/gilli isogenic clone LG-15, we have adapted a system that consists in transplanting 15/0 tumor cells embedded into rat collagen under the dorsal skin of LG-15 tadpole recipients. This system recapitulates many facets of mammalian tumorigenesis and permits real time visualization of the active formation of the tumor microenvironment induced by 15/0 tumor cells including neovascularization, collagen rearrangements as well as infiltration of immune cells and melanophores.
肿瘤具有在体内作为一个自我维持的实体生长的能力。这种自主性部分是通过肿瘤细胞诱导新血管形成(血管生成)的能力以及控制肿瘤块内细胞运输来实现的。这些能力极大地降低了许多癌症治疗的效果,并对开发更有效的癌症治疗方法构成挑战。因此,需要适合直接显微镜观察血管形成和细胞运输的动物模型,特别是在肿瘤形成的早期阶段。在这里,我们在两栖动物非洲爪蟾的蝌蚪中开发了一种可靠且经济高效的肿瘤模型系统。蝌蚪因其体积小和透明度高而非常适合直接显微镜观察。使用源自非洲爪蟾/吉利同基因克隆LG-15并可移植到其中的胸腺淋巴瘤细胞系15/0,我们改进了一种系统,该系统包括将包埋在大鼠胶原蛋白中的15/0肿瘤细胞移植到LG-15蝌蚪受体的背部皮肤下。该系统概括了哺乳动物肿瘤发生的许多方面,并允许实时可视化由15/0肿瘤细胞诱导的肿瘤微环境的活跃形成,包括新血管形成、胶原重排以及免疫细胞和黑素细胞的浸润。