Shi Rongchen, Xiang Wei, Kang Xia, Zhang Lili, Wang Jinping, Miao Hongming, He Fengtian
Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, China.
Department of Military Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing 400038, China.
J Cancer. 2019 Jan 1;10(2):367-377. doi: 10.7150/jca.27947. eCollection 2019.
Colorectal cancer (CRC) usually gives rise to transcoelomic spread and ultimately causes peritoneal carcinomatosis (PC). However, mechanism studies, especially the immunological basis of colorectal PC, are rarely revealed due to lack of a suitable PC model. Here we selected a mouse colorectal cancer cell line MC-38 for intraperitoneal inoculation in the C57BL/6 mice to mimic the development of colorectal PC. We demonstrated that the injected CRC cells preferentially and rapidly migrated and colonized in the visceral fat tissues, but not in other visceral organs. With flow cytometric analysis, we found the proportions of spleen T cells and B cells were not affected by PC progression, while the ratios of blood CD4+ and CD8+ T cells were largely influenced. Especially, the quantity or activity of CD4+ and CD8+ T cells in visceral fats were intimately regulated by PC development. Taken together, we successfully constructed a colorectal PC model in immune-competent mice and revealed the alteration of adaptive immunity in PC development. Our study might potentiate the research and therapy strategies of colorectal PC.
结直肠癌(CRC)通常会引发经体腔播散,最终导致腹膜癌病(PC)。然而,由于缺乏合适的PC模型,机制研究,尤其是结直肠癌PC的免疫基础研究很少被揭示。在这里,我们选择了一种小鼠结肠癌细胞系MC-38,将其腹腔接种到C57BL/6小鼠体内,以模拟结直肠癌PC的发展。我们证明,注射的CRC细胞优先且迅速地迁移并定植在内脏脂肪组织中,而不是其他内脏器官中。通过流式细胞术分析,我们发现脾脏T细胞和B细胞的比例不受PC进展的影响,而血液中CD4+和CD8+ T细胞的比例受到很大影响。特别是,内脏脂肪中CD4+和CD8+ T细胞的数量或活性受到PC发展的密切调节。综上所述,我们在免疫健全的小鼠中成功构建了结直肠癌PC模型,并揭示了PC发展过程中适应性免疫的改变。我们的研究可能会加强结直肠癌PC的研究和治疗策略。