Akporiaye E T, Stewart S J, Stevenson A P, Stewart C C
Cancer Res. 1985 Dec;45(12 Pt 1):6457-62.
This study examined the recruitment of host cells into a progressing EMT6 tumor following the inoculation of tumorigenic cells into a preimplanted gelatin sponge. Tumor cell proliferation occurred to a greater extent in sponge tumors than in tumors obtained by direct subcutaneous injection of tumor cells. Blank sponges, lacking tumorigenic cells and used as controls, elicited an inflammatory response characterized by a modest infiltration of granulocytes and macrophages whose numbers, after Day 7 postimplantation, remained unchanged for 21 days of sponge residence in the animal. In contrast, when the sponge contained tumor cells, there was a continuous increase in host cell infiltration that paralleled the increase in tumor cells. Whether in a sponge or not, tumor cells represented more than half of the recovered cells by Day 21 after tumor cell inoculation. Macrophages comprised the greatest fraction of host cells infiltrating the tumors. Flow cytometric analysis and morphological examination of disaggregated tumors indicated that macrophages (19-51%) made up the largest proportion of host cells followed in order by granulocytes (6-18%) and lymphocytes (2-9%). Sorting of marker-labeled cells revealed that 94% of the surface immunoglobulin-bearing cells were macrophages. Twenty-two % of the cells bearing the Thy 1.2 marker were lymphocytes, and 68% were macrophages. The data confirm the occurrence of a cellular host response in the tumor-bearing animal which is distinct from the foreign body reaction elicited by a blank sponge. Additionally, the sponge system described here represents a recoverable environment that would facilitate the study of in vivo host-tumor cell interactions that occur during early tumor development or later during therapy-induced tumor rejection when a palpable tumor is not present.
本研究检测了将致瘤细胞接种到预先植入的明胶海绵后,宿主细胞向进展期EMT6肿瘤的募集情况。海绵肿瘤中的肿瘤细胞增殖程度比直接皮下注射肿瘤细胞所形成的肿瘤更高。不含致瘤细胞的空白海绵用作对照,引发了以粒细胞和巨噬细胞适度浸润为特征的炎症反应,植入后第7天,海绵在动物体内留存21天期间,其数量保持不变。相比之下,当海绵含有肿瘤细胞时,宿主细胞浸润持续增加,与肿瘤细胞的增加平行。无论有无海绵,接种肿瘤细胞后第21天,肿瘤细胞占回收细胞的一半以上。巨噬细胞是浸润肿瘤的宿主细胞中比例最大的部分。对解离肿瘤进行的流式细胞术分析和形态学检查表明,巨噬细胞(19% - 51%)在宿主细胞中占比最大,其次是粒细胞(6% - 18%)和淋巴细胞(2% - 9%)。对标记有标志物的细胞进行分选显示,94%的表面带有免疫球蛋白的细胞是巨噬细胞。带有Thy 1.2标志物的细胞中,22%是淋巴细胞,68%是巨噬细胞。这些数据证实了荷瘤动物中存在细胞宿主反应,这与空白海绵引发的异物反应不同。此外,本文所述的海绵系统代表了一种可回收的环境,将有助于研究早期肿瘤发展过程中或后期治疗诱导肿瘤排斥(此时不存在可触及的肿瘤)期间发生的体内宿主 - 肿瘤细胞相互作用。