期刊
CELL REPORTS
卷 36, 期 10, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.109674
关键词
-
类别
资金
- Stowers Institute for Medical Research [SIMR-1004]
- NCI Cancer Center Support Grant [P30 CA168524]
- NIH [U01DK085507]
- NIDDK
- NIAID
The study reveals a bidirectional crosstalk between treatment-resistant tumor-initiating stem cells (TrTSC) and the tumor microenvironment (TME), leading to a contexture that promotes tumor growth and immunosuppression.
Tumor-initiating stem cells (TSCs) are critical for drug resistance and immune escape. However, the mutual regulations between TSC and tumor microenvironment (TME) remain unclear. Using DNA-label retaining, single-cell RNA sequencing (scRNA-seq), and other approaches, we investigated intestinal adenoma in response to chemoradiotherapy (CRT), thus identifying therapy-resistant TSCs (TrTSCs). We find bidirectional crosstalk between TSCs and TME using CellPhoneDB analysis. An intriguing finding is that TSCs shape TME into a landscape that favors TSCs for immunosuppression and propagation. Using adenoma-organoid co-cultures, niche-cell depletion, and lineaging tracing, we characterize a functional role of cyclooxygenase2 (Cox-2)-dependent signaling, predominantly occurring between tumor-associated monocytes and macrophages (TAMMs) and TrTSCs. We show that TAMMs promote TrTSC proliferation through prostaglandin E2 (PGE2)-PTGER4(EP4) signaling, which enhances beta-catenin activity via AKT phosphorylation. Thus, our study shows that the bidirectional crosstalk between TrTSC and TME results in a pro-tumorigenic and immunosuppressive contexture.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据