Sakimoto Yuri, Kumegawa Kohei, Matsui Shimpei, Yamaguchi Tomohiro, Mukai Toshiki, Okabayashi Koji, Mori Seiichi, Kitagawa Yuko, Akiyoshi Takashi, Maruyama Reo
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Project for Cancer Epigenomics, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
BJC Rep. 2024 Nov 18;2(1):88. doi: 10.1038/s44276-024-00112-3.
Peritoneal metastasis, a major complication of colorectal cancer (CRC), often leads to poor quality of life and unfavorable outcomes. Despite numerous studies characterizing its biological features in CRC, intratumor heterogeneity and interactions between cancer cells and tumor microenvironment cells remain poorly understood.
To explore these aspects, we performed single-cell transcriptome analysis of matched primary tumor and peritoneal metastasis samples from a treatment-naïve patient.
Our analysis revealed enrichment of "tip" endothelial cells in the primary tumor, driving angiogenic sprouting, whereas these cells were absent in peritoneal metastases. Moreover, cancer cells in peritoneal metastasis displayed a distinct expression signature associated with epithelial-mesenchymal transition and tumor invasiveness. Analysis of cell-cell communication between endothelial and tumor cells revealed decreased VEGF signaling and increased CXCL-ACKR1 interactions in peritoneal metastasis.
Although limited by its N-of-1 design and requiring further validation, our study provides preliminary observations suggesting that alterations in cancer-endothelial cell interactions could reduce dependence on VEGF signaling and influence immune cell infiltration in CRC peritoneal metastasis.
腹膜转移是结直肠癌（CRC）的主要并发症，常导致生活质量下降和不良预后。尽管有许多研究对其在CRC中的生物学特征进行了描述，但肿瘤内异质性以及癌细胞与肿瘤微环境细胞之间的相互作用仍知之甚少。
为了探究这些方面，我们对一名未经治疗的患者的配对原发性肿瘤和腹膜转移样本进行了单细胞转录组分析。
我们的分析显示，原发性肿瘤中“顶端”内皮细胞富集，驱动血管生成芽生，而这些细胞在腹膜转移中不存在。此外，腹膜转移中的癌细胞表现出与上皮-间质转化和肿瘤侵袭相关的独特表达特征。对内皮细胞和肿瘤细胞之间的细胞间通讯分析显示，腹膜转移中VEGF信号传导减少，CXCL-ACKR1相互作用增加。
尽管受限于单病例设计且需要进一步验证，但我们的研究提供了初步观察结果，表明癌症-内皮细胞相互作用的改变可能会降低对VEGF信号传导的依赖性，并影响CRC腹膜转移中的免疫细胞浸润。
