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癌细胞与成纤维细胞通过肝素结合表皮生长因子（HB-EGF）、表皮生长因子受体（EGFR）和丝裂原活化蛋白激酶（MAPK）信号通路的相互作用促进了巨噬细胞趋化因子在鳞状细胞癌中的表达。

Cancer cell - Fibroblast crosstalk via HB-EGF, EGFR, and MAPK signaling promotes the expression of macrophage chemo-attractants in squamous cell carcinoma.

作者信息

Giangreco Giovanni, Rullan Antonio, Naito Yutaka, Biswas Dhruva, Liu Yun-Hsin, Hooper Steven, Nenclares Pablo, Bhide Shreerang, Chon U Cheang Maggie, Chakravarty Probir, Hirata Eishu, Swanton Charles, Melcher Alan, Harrington Kevin, Sahai Erik

机构信息

Tumour Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.

Department of Radiotherapy and Imaging, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.

出版信息

iScience. 2024 Aug 3;27(9):110635. doi: 10.1016/j.isci.2024.110635. eCollection 2024 Sep 20.

DOI:10.1016/j.isci.2024.110635
PMID:39262776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11387794/
Abstract

Interactions between cells in the tumor microenvironment (TME) shape cancer progression and patient prognosis. To gain insights into how the TME influences cancer outcomes, we derive gene expression signatures indicative of signaling between stromal fibroblasts and cancer cells, and demonstrate their prognostic significance in multiple and independent squamous cell carcinoma cohorts. By leveraging information within the signatures, we discover that the HB-EGF/EGFR/MAPK axis represents a hub of tumor-stroma crosstalk, promoting the expression of CSF2 and LIF and favoring the recruitment of macrophages. Together, these analyses demonstrate the utility of our approach for interrogating the extent and consequences of TME crosstalk.

摘要

肿瘤微环境（TME）中的细胞间相互作用塑造了癌症进展和患者预后。为深入了解TME如何影响癌症结局，我们得出了指示基质成纤维细胞与癌细胞之间信号传导的基因表达特征，并在多个独立的鳞状细胞癌队列中证明了它们的预后意义。通过利用这些特征中的信息，我们发现HB-EGF/EGFR/MAPK轴代表肿瘤-基质相互作用的枢纽，促进CSF2和LIF的表达并有利于巨噬细胞的募集。总之，这些分析证明了我们的方法在探究TME相互作用的程度和后果方面的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/5ff334329b07/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/9b071c141176/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/6ec1e3bd4741/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/dbc3a119ec22/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/c415ab55bc19/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/470f61297136/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/5ff334329b07/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/9b071c141176/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/6ec1e3bd4741/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/dbc3a119ec22/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/c415ab55bc19/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/470f61297136/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b98/11387794/5ff334329b07/gr5.jpg

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本文引用的文献

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EGFR-activated myofibroblasts promote metastasis of pancreatic cancer.表皮生长因子受体激活的肌成纤维细胞促进胰腺癌转移。
Cancer Cell. 2024 Jan 8;42(1):101-118.e11. doi: 10.1016/j.ccell.2023.12.002. Epub 2023 Dec 28.
2
Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression.致癌性 KRAS 驱动脂肪纤维生成以促进血管生成和结肠癌进展。
Cancer Discov. 2023 Dec 12;13(12):2652-2673. doi: 10.1158/2159-8290.CD-22-1467.
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The evolution of lung cancer and impact of subclonal selection in TRACERx.肺癌的演变及 TRACERx 中亚克隆选择的影响。
Nature. 2023 Apr;616(7957):525-533. doi: 10.1038/s41586-023-05783-5. Epub 2023 Apr 12.
4
Single-cell transcriptome profiling of the stepwise progression of head and neck cancer.单细胞转录组谱分析头颈部癌的逐步进展。
Nat Commun. 2023 Feb 24;14(1):1055. doi: 10.1038/s41467-023-36691-x.
5
Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment.通过肿瘤微环境的免疫调节来改善头颈部癌症的治疗方法。
Nat Rev Cancer. 2023 Mar;23(3):173-188. doi: 10.1038/s41568-022-00531-9. Epub 2022 Dec 1.
6
RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma.RAS 致癌活性可预测肺腺癌对化疗的反应和预后。
Nat Commun. 2022 Sep 26;13(1):5632. doi: 10.1038/s41467-022-33290-0.
7
Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors.癌症相关成纤维细胞的空间定位和基质程序促进人肺肿瘤中的 T 细胞排斥。
Cancer Discov. 2022 Nov 2;12(11):2606-2625. doi: 10.1158/2159-8290.CD-21-1714.
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Cell type and gene expression deconvolution with BayesPrism enables Bayesian integrative analysis across bulk and single-cell RNA sequencing in oncology.贝叶斯棱镜可实现细胞类型和基因表达的去卷积，从而能够在肿瘤的批量和单细胞 RNA 测序中进行贝叶斯综合分析。
Nat Cancer. 2022 Apr;3(4):505-517. doi: 10.1038/s43018-022-00356-3. Epub 2022 Apr 25.
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Single-cell and spatial analysis reveal interaction of FAP fibroblasts and SPP1 macrophages in colorectal cancer.单细胞和空间分析揭示结直肠癌中 FAP 成纤维细胞和 SPP1 巨噬细胞的相互作用。
Nat Commun. 2022 Apr 1;13(1):1742. doi: 10.1038/s41467-022-29366-6.
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