Kawaguchi T, Kawaguchi M, Miner K M, Lembo T M, Nicolson G L
Clin Exp Metastasis. 1983 Jul-Sep;1(3):247-59. doi: 10.1007/BF00736408.
The murine melanoma subline B16-F1 of low brain- and lung-colonizing potential has been used to obtain brain-colonizing variant sublines by sequential selection in vivo for their abilities to form brain meningeal tumors. After fourteen and fifteen selections in syngeneic C57BL/6 mice sublines B16-B14b and B16-B15b, respectively, were established in culture. These were then assayed in vivo by injection of single tumor cell suspensions into the tail vein (i.v.), left ventricle of the heart (i.c.) or left common carotid artery (i.a.), and the resulting tumors were examined histologically. Injection of subline B16-B14b or B16-B15b resulted in brain meningeal tumor formation in the dura mater and leptomeninges with invasion into underlying brain parenchyma and also some brain ventricular tumors at the sites of i.a. injection. Lung colonization ability remained in the brain-selected sublines, although it was remarkably reduced in i.a. tumor cell-injected animals. The brain meningeal tumors that formed were of three types: intravascular, nodular or infiltrative. Injection of tumor cells i.v. resulted mainly in the establishment of the intravascular type of brain meningeal tumors with eventual perivascular invasion, while injection i.a. or i.c. resulted mostly in nodular or infiltrative type brain meningeal tumors. The B16-B14b brain meningeal tumors formed were small (less than 1 mm in diameter) and usually nonpigmented, while B16-B15b tumors were generally large (up to 7 mm in diameter) and pigmented. Host reactions towards B16-B14b and B16-B15b tumors at meningeal sites differed. The former B16 subline was characterized by extensive fibrosis with some immunocytic cell infiltration in and around the meningeal tumors, while the latter subline did not elicit such host reactions. In contrast, tumors in brain parenchyma failed to evoke observable host reactions, and there was little evidence of immunocyte cell infiltration or glial cell alterations.
具有低脑和肺定植潜力的小鼠黑色素瘤亚系B16-F1已被用于通过在体内连续选择其形成脑脑膜肿瘤的能力来获得脑定植变异亚系。在同基因C57BL/6小鼠中分别进行14次和15次选择后，亚系B16-B14b和B16-B15b在培养物中建立。然后通过将单个肿瘤细胞悬液经尾静脉（静脉内）、心脏左心室（脑内）或左颈总动脉（动脉内）注射在体内进行检测，并对产生的肿瘤进行组织学检查。注射亚系B16-B14b或B16-B15b导致硬脑膜和软脑膜形成脑脑膜肿瘤，并侵入下层脑实质，在动脉内注射部位也有一些脑室肿瘤。脑选择的亚系中仍保留肺定植能力，尽管在动脉内注射肿瘤细胞的动物中该能力显著降低。形成的脑脑膜肿瘤有三种类型：血管内型、结节型或浸润型。静脉内注射肿瘤细胞主要导致血管内型脑脑膜肿瘤的形成，并最终发生血管周围浸润，而动脉内或脑内注射大多导致结节型或浸润型脑脑膜肿瘤。形成的B16-B14b脑脑膜肿瘤较小（直径小于1毫米），通常无色素沉着，而B16-B15b肿瘤一般较大（直径可达7毫米）且有色素沉着。宿主对脑膜部位B16-B14b和B16-B15b肿瘤的反应不同。前一个B16亚系的特征是广泛纤维化，脑膜肿瘤内及其周围有一些免疫细胞浸润，而后一个亚系未引发此类宿主反应。相比之下，脑实质内的肿瘤未能引起可观察到的宿主反应，几乎没有免疫细胞浸润或神经胶质细胞改变的证据。
