Di Carlo E, Modesti A, Castrilli G, Landuzzi L, Allione A, de Giovanni C, Musso T, Musiani P
Istituto di Patologia Umana e Medicina Sociale, Università G. D'Annunzio, Italy.
J Pathol. 1997 May;182(1):76-85. doi: 10.1002/(SICI)1096-9896(199705)182:1<76::AID-PATH805>3.0.CO;2-B.
Cells from the spontaneous metastatic TSA mammary adenocarcinoma of BALB/C mouse were transfected with the murine (interleukin-6) IL6 gene. The clone (TSA-IL6) secreting the largest amount of IL6 displayed an in vitro increased growth rate compared with that of TSA cells transfected with the neomycin resistance gene only (TSA-neo). TSA-IL6 cell colonies consisted mainly of fusiform cells and TSA-neo colonies of polygonal cells. When subcutaneously (s.c.) injected in syngeneic mice, TSA-IL6 cells gave rise to tumours that grew significantly slower than TSA-neo cell tumours. Microscopically, TSA-IL6 tumours displayed a fascicular pattern of growth, associated with a very scanty macrophage infiltrate. S.c. TSA-IL6 tumours were significantly less metastatic than TSA-neo tumours. By contrast, following intravenous (i.v.) challenge, TSA-IL6 cells produced 5-7 times more lung metastases than TSA-neo cells. The i.v. TSA-IL6 cell lung metastases showed a marked macrophage infiltrate and a rich vascularization. The high in vitro TSA-IL6 cell growth rate is attributable to the IL6-induced production of growth factors, some of which possess heparin-binding properties, such as amphiregulin. The differences in vascularization and macrophage infiltrate may underlie the observed differences between s.c. TSA-IL6 tumour growth with low spontaneous metastatic potential and the widespread growth of i.v. metastasis.
用小鼠白细胞介素-6（IL6）基因转染来自BALB/C小鼠自发性转移的TSA乳腺腺癌的细胞。与仅转染新霉素抗性基因的TSA细胞（TSA-neo）相比，分泌大量IL6的克隆（TSA-IL6）在体外显示出更高的生长速率。TSA-IL6细胞集落主要由梭形细胞组成，而TSA-neo集落由多边形细胞组成。当同基因小鼠皮下注射时，TSA-IL6细胞产生的肿瘤生长明显比TSA-neo细胞肿瘤慢。显微镜下，TSA-IL6肿瘤呈束状生长模式，巨噬细胞浸润极少。皮下注射的TSA-IL6肿瘤的转移能力明显低于TSA-neo肿瘤。相比之下，静脉注射后，TSA-IL6细胞产生的肺转移灶比TSA-neo细胞多5至7倍。静脉注射的TSA-IL6细胞肺转移灶显示出明显的巨噬细胞浸润和丰富的血管形成。TSA-IL6细胞在体外的高生长速率归因于IL6诱导的生长因子产生，其中一些生长因子具有肝素结合特性，如双调蛋白。血管形成和巨噬细胞浸润的差异可能是皮下注射的具有低自发转移潜力的TSA-IL6肿瘤生长与静脉注射转移的广泛生长之间观察到的差异的基础。
