Vol'pe E A
Biull Eksp Biol Med. 1991 Nov;112(11):525-9.
We have previously shown that in vitro cocultivation of the low-malignant spontaneously transformed in vitro cells of STHE strain with LPS-activated peritoneal exudate cells (PECa) of normal Syrian hamsters resulted (in contrast to resident PEC (PECr)) in selection of the STHE cell variants resistant to macrophage- and hydrogen peroxide (H2O2)-mediated cytotoxic activity (CTA). In the present study the malignant characteristics, i.e. tumorigenic and metastasizing activities (TGA, MA), of the STHE cell variants in vitro selected with PECa and PECr as well as the parental ones were compared. By the use of quantitative transplantation test the relatively increased level of TGA of the STHE cell variants selected with PECa, especially on the late stages of in vitro selection, has been demonstrated. The increase of the tumour size of transplanted cells was demonstrated after in vitro selection of parental STHE cells with either PECa of PECr. The mean number of spontaneous lung metastases at 60th day after s.c. transplantation of the cell variants selected with PECa and PECr was increased as compared to parental STHE cells, however, as a rule, did not exceed 20-25. The study of experimental MA revealed that only STHE cell variants selected with PECa were able to form significantly larger numbers of experimental lung metastases, what was more expressed after the 4th, 5th and 10th cycles of the selection procedure. Thus, activated REC (mainly macrophages and lymphocytes) are capable to select in vitro tumour cell variants characterized with not only increased resistance to CTA of the macrophages and H2O2, but also more tumorigenic and metastasizing, i.e. more malignant.
我们之前已经表明,将STHE株低恶性自发转化的体外细胞与正常叙利亚仓鼠经脂多糖(LPS)激活的腹腔渗出细胞(PECa)进行体外共培养,结果(与驻留腹腔渗出细胞(PECr)相反)筛选出了对巨噬细胞和过氧化氢(H2O2)介导的细胞毒活性(CTA)具有抗性的STHE细胞变体。在本研究中,比较了用PECa和PECr以及亲代细胞体外筛选出的STHE细胞变体的恶性特征,即致瘤活性和转移活性(TGA、MA)。通过定量移植试验表明,用PECa筛选出的STHE细胞变体的TGA水平相对升高,尤其是在体外筛选的后期。在用PECa或PECr对亲代STHE细胞进行体外筛选后,移植细胞的肿瘤大小增加。与亲代STHE细胞相比,用PECa和PECr筛选出的细胞变体在皮下移植后第60天的自发性肺转移平均数量增加,但通常不超过20 - 25个。对实验性转移活性的研究表明,只有用PECa筛选出的STHE细胞变体能够形成数量明显更多的实验性肺转移灶,在筛选程序的第4、5和10个周期后这种现象更明显。因此,活化的REC(主要是巨噬细胞和淋巴细胞)能够在体外筛选出不仅对巨噬细胞的CTA和H2O2具有更高抗性,而且具有更强致瘤性和转移性,即更具恶性的肿瘤细胞变体。