Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Zhejiang, Hangzhou, China.
Department of Pharmacy, Zhejiang Provincial People's Hospital Bijie Hospital, Bijie, Guizhou, China.
J Cell Mol Med. 2024 Oct;28(20):e70142. doi: 10.1111/jcmm.70142.
Distal metastases result from metastatic microenvironment and tumour epithelial cell interactions, the cellular heterogeneity of primary colorectal cancer (CRC) and liver metastases (LM) was evaluated by integrating single-cell sequencing data, and the collected gene expression data from metastatic epithelial cell subsets was used to construct a prognostic model and to identify intercellular receptor-ligand interactions between epithelial and immune cells in CRC and LM. Multiplex immunofluorescence staining, and in vitro wound healing, cell migration and cell apoptosis assays were performed to further explore the biological relevance of identified potential regulatory molecules. In this study, approximately 17 epithelial cell subtypes were detected, with Epi-11 cells being highly expressed in LM tissues compared with CRC samples. Furthermore, patients with high expression of the metastasis-related genetic profile of Epi-11 had a poorer prognosis. By predicting receptor-ligand interactions, Epi-11 cells were found to interact more with myeloid and T/natural killer cells in LM tissues when compared to primary CRC samples, which was mediated by the PLXNB1/SEMA4D axis. In addition, high SEMA4D expression was correlated with decreased overall survival of patients with CRC, whereas PLXNB1 was not. SEMA4D knockdown prevented the migration and promoted the apoptosis of HCT116 cells in vitro. In summary, Epi-11 cells, an important subset of epithelial cells, may drive the LM of CRC and act by crosstalk with immune cells through the PLXNB1/SEMA4D signalling axis.
远处转移是由转移微环境和肿瘤上皮细胞相互作用引起的，通过整合单细胞测序数据，评估了原发性结直肠癌 (CRC) 和肝转移 (LM) 的肿瘤细胞异质性，并利用转移性上皮细胞亚群的基因表达数据构建了一个预后模型，鉴定了 CRC 和 LM 中上皮细胞和免疫细胞之间的细胞间受体-配体相互作用。进行了多重免疫荧光染色、体外划痕愈合、细胞迁移和细胞凋亡检测，以进一步探索鉴定的潜在调控分子的生物学相关性。在这项研究中，检测到大约 17 种上皮细胞亚型，Epi-11 细胞在 LM 组织中的表达明显高于 CRC 样本。此外，Epi-11 高表达转移相关基因谱的患者预后较差。通过预测受体-配体相互作用，与原发性 CRC 样本相比，Epi-11 细胞在 LM 组织中与髓样细胞和 T/自然杀伤细胞的相互作用更多，这是由 PLXNB1/SEMA4D 轴介导的。此外，SEMA4D 的高表达与 CRC 患者的总生存率降低相关，而 PLXNB1 则没有。SEMA4D 敲低可防止 HCT116 细胞在体外的迁移并促进其凋亡。总之，Epi-11 细胞是上皮细胞的一个重要亚群，可能通过 PLXNB1/SEMA4D 信号轴与免疫细胞相互作用来驱动 CRC 的 LM。
