Furukawa T, Fu X, Kubota T, Watanabe M, Kitajima M, Hoffman R M
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Cancer Res. 1993 Mar 1;53(5):1204-8.
Nude mice have been used to develop s.c. growing human stomach tumors, but these rarely metastasize. Recently, I. J. Fidler and others have developed orthotopic implantation metastatic models using cell suspensions which are inoculated into the corresponding organ of nude mice from which the tumor cells were originally derived in the human. However, recent work has indicated that disaggregated cell suspensions may not always express their full metastatic potential. In this light, we have recently developed an orthotopic implant model utilizing intact tissue such as that obtained directly from surgery. This approach has yielded high take rates and frequent metastases in colon cancer, bladder cancer, lung cancer, pancreatic cancer, and prostate cancer. We report here the application of this intact tissue orthotopic implant technique to stomach cancer resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject stomach cancer cells at the same site, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of using intact tissue to allow full expression of metastatic potential. Injuring the serosa similar to that occurring in intact tissue transplantation did not increase the metastatic rate after orthotopic injection of cell suspensions of stomach tumor cells. This intact tissue orthotopic implantation model should allow development of new treatment modalities and further study of the biology of human stomach cancer.
裸鼠已被用于培育皮下生长的人胃肿瘤，但这些肿瘤很少发生转移。最近，I. J. 菲德勒等人利用细胞悬液开发了原位植入转移模型，将细胞悬液接种到裸鼠的相应器官中，这些器官是人类肿瘤细胞最初来源的部位。然而，最近的研究表明，分散的细胞悬液可能并不总是能充分发挥其转移潜能。鉴于此，我们最近开发了一种利用完整组织（如直接从手术中获取的组织）的原位植入模型。这种方法在结肠癌、膀胱癌、肺癌、胰腺癌和前列腺癌中产生了高接种率和频繁的转移。我们在此报告这种完整组织原位植入技术在胃癌中的应用，结果在100%的小鼠中形成了转移，原发肿瘤广泛生长至区域淋巴结、肝脏和肺。相比之下，当使用细胞悬液在同一部位注射胃癌细胞时，只有6.7%形成局部肿瘤的小鼠发生了转移，这强调了使用完整组织以充分发挥转移潜能的重要性。在原位注射胃肿瘤细胞悬液后，类似于完整组织移植中发生的浆膜损伤并没有增加转移率。这种完整组织原位植入模型应有助于开发新的治疗方法，并进一步研究人类胃癌的生物学特性。
