PO.TB10.15 · 肿瘤生物学
由器官间串扰介导的肿瘤纤维化新机制
Novel mechanism of tumor fibrosis mediated by interorgan crosstalk
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
弥漫型胃癌（DGC）通过 PDGF/PDGFR 信号在癌症相关成纤维细胞（CAFs）与癌细胞之间表现出强烈的相互作用。虽然 PDGFR 在 CAFs 中表达，但 PDGF 配体此前被认为主要由癌细胞分泌。然而，DGC 队列分析揭示了基质纤维化与血小板聚集之间的相关性，提示血小板可能作为一种替代的 PDGF 来源。本研究旨在阐明通过 GC 纤维化-骨髓（BM）造血-血小板轴的器官间串扰机制。IL6 在 DGC 中尤为上调，并与纤维化相关。我们使用 IL6 过表达的鼠源 GC 细胞建立了原位模型，这些细胞发展为纤维化肿瘤。值得注意的是，这些小鼠外周血中的血小板显示出计数、体积和 PDGFD 浓度的增加。BM 中的细胞群分析揭示了巨核细胞祖细胞增加和红系祖细胞减少，提示 IL6 诱导的造血失衡。这些发现提示，IL6 促进富含 PDGFD 的血小板生成，从而促进肿瘤纤维化。本研究强调了 BM 来源的血小板在增强 DGC 肿瘤纤维化中的关键作用。
查看英文原文 English abstract
Diffuse-type gastric cancer (DGC) shows strong interactions between cancer-associated fibroblasts (CAFs) and cancer cells through PDGF/PDGFR signaling. While PDGFR is expressed in CAFs, PDGF ligands were believed to be mainly secreted by cancer cells. However, DGC cohort analysis revealed a correlation between stromal fibrosis and platelet aggregation, suggesting that platelets may serve as an alternative PDGF source. This study aims to elucidate the mechanisms of interorgan crosstalk through GC fibrosis-bone marrow (BM) hematopoiesis-platelet axis. IL6 was particularly upregulated in DGC and correlated with fibrosis. We established an orthotopic model using IL6-overexpressing murine GC cells, which developed fibrotic tumors. Notably, platelets in peripheral blood of these mice showed increased count, size, and PDGFD concentration. Cell population analysis in BM revealed increased megakaryocyte progenitors and decreased erythroid progenitors, indicating IL6-induced hematopoietic imbalance. These findings suggest that IL6 promotes PDGFD-rich platelet production, contributing to tumor fibrosis. This study highlights a key role of BM-derived platelets to enhance tumor fibrosis in DGC.
利益披露 Disclosure
A. Nishimura, None..
T. Ishimoto, None..
A. Yonemura, None.