Topley P, Jenkins D C, Jessup E A, Stables J N
Department of Cell Biology, Wellcome Research Laboratories, Beckenham, Kent, UK.
Br J Cancer. 1993 May;67(5):953-8. doi: 10.1038/bjc.1993.176.
Previous reports have indicated that reconstituted basement membrane (matrigel), when co-injected with either established or primary human tumour cells, can improve the growth of subcutaneous xenografts in nude mice. The human adenocarcinoma cell lines A549, SW480, and WiDr, and the human fibrosarcoma cell line HT1080scc2 exhibit varying degrees of tumourigenicity in nude mice. All these lines showed increased tumorigenicity and/or growth rate, together with a change towards a more differentiated tissue morphology, when co-injected with matrigel into nude mice. Experiments using A549 cell line have indicated that the effect of matrigel is concentration-dependent and that increased growth rate is not maintained when xenografts grown with matrigel are passaged into further mice. These results strongly suggest that increased tumour growth results from the improved growth conditions afforded by matrigel, rather than from the selection of subpopulations of the most tumourigenic cells. Increased growth of intracaecal tumours arising from the co-injection of SW480 cells with matrigel, indicate a possible use for matrigel in the development of more relevant animal models using the orthotopic site. Purified laminin significantly increased the growth of sc tumours resultant from co-injection with either WiDr or A549 cells, whereas collagen IV or laminin with entactin showed no such effect. A role for free laminin in the stimulation of cell growth in the absence of an intact basement membrane is discussed.
先前的报告表明,重组基底膜(基质胶)与已建立的或原代人肿瘤细胞共同注射时,可促进裸鼠皮下异种移植物的生长。人腺癌细胞系A549、SW480和WiDr,以及人纤维肉瘤细胞系HT1080scc2在裸鼠中表现出不同程度的致瘤性。当与基质胶共同注射到裸鼠体内时,所有这些细胞系均显示出致瘤性增加和/或生长速率提高,同时组织形态向更分化的方向转变。使用A549细胞系进行的实验表明,基质胶的作用具有浓度依赖性,并且当用基质胶培养的异种移植物传代到其他小鼠体内时,生长速率的增加无法维持。这些结果强烈表明,肿瘤生长增加是由于基质胶提供了更好的生长条件,而不是由于选择了最具致瘤性的细胞亚群。SW480细胞与基质胶共同注射导致盲肠内肿瘤生长增加,这表明基质胶在利用原位部位开发更相关动物模型方面可能具有应用价值。纯化的层粘连蛋白显著促进了与WiDr或A549细胞共同注射所产生的皮下肿瘤的生长,而IV型胶原蛋白或层粘连蛋白与巢蛋白的组合则没有这种作用。本文讨论了游离层粘连蛋白在缺乏完整基底膜时对细胞生长的刺激作用。