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癌症腹膜转移的细胞生物学:多克隆播种与腹膜肿瘤微环境

Cell Biology of Cancer Peritoneal Metastasis: Multiclonal Seeding and Peritoneal Tumor Microenvironment.

作者信息

Yamaguchi Hideki, Miyazaki Makoto

机构信息

Department of Cancer Cell Research, Sasaki Institute, Sasaki Foundation, Tokyo, Japan.

出版信息

Cancer Sci. 2025 May;116(5):1171-1180. doi: 10.1111/cas.70021. Epub 2025 Feb 13.

DOI:10.1111/cas.70021
PMID:39948828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12044651/
Abstract

Peritoneal metastasis, also known as peritoneal dissemination or carcinomatosis, refers to the spread of cancer to the peritoneum that lines the abdominal and pelvic cavities and covers the abdominal organs. Peritoneal metastasis typically occurs in advanced cancers of abdominal origin, most commonly gastrointestinal and gynecological cancers. Conventional chemotherapy has limited efficacy, and no effective molecular-targeted therapy is currently available for peritoneal metastasis. As a result, peritoneal metastasis is associated with poor outcomes and significantly reduced quality of life in patients with advanced cancers. This is largely due to a limited understanding of the molecular and cellular mechanisms underlying peritoneal metastasis. However, recent studies employing innovative approaches have provided novel insights into the mechanisms of peritoneal metastasis, contributing to the development of novel therapeutic strategies. In this review, we summarize recent findings on the cell biological aspects of peritoneal metastasis and potential therapeutic target molecules. In particular, we emphasize the importance of cancer cell clustering within the abdominal cavity, which drives multiclonal peritoneal seeding. We also focus on the interactions of cancer cells with mesothelial cells and cancer-associated fibroblasts within the peritoneal tumor microenvironment.

摘要

腹膜转移,也称为腹膜播散或癌性腹膜炎,是指癌症扩散至覆盖腹腔和盆腔并包裹腹部器官的腹膜。腹膜转移通常发生于起源于腹部的晚期癌症,最常见的是胃肠道和妇科癌症。传统化疗疗效有限,目前尚无针对腹膜转移的有效分子靶向治疗方法。因此,腹膜转移与晚期癌症患者的不良预后及生活质量显著下降相关。这在很大程度上是由于对腹膜转移潜在的分子和细胞机制了解有限。然而,最近采用创新方法进行的研究为腹膜转移机制提供了新的见解,有助于开发新的治疗策略。在本综述中,我们总结了腹膜转移细胞生物学方面的最新发现以及潜在的治疗靶点分子。特别强调了癌细胞在腹腔内聚集的重要性,这推动了多克隆腹膜种植。我们还关注癌细胞与腹膜肿瘤微环境中的间皮细胞和癌症相关成纤维细胞之间的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/c5345fafa5d9/CAS-116-1171-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/31bca0e6af9d/CAS-116-1171-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/4bf36d10dbca/CAS-116-1171-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/47bb77b589fe/CAS-116-1171-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/c5345fafa5d9/CAS-116-1171-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/31bca0e6af9d/CAS-116-1171-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/4bf36d10dbca/CAS-116-1171-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/47bb77b589fe/CAS-116-1171-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8e3/12044651/c5345fafa5d9/CAS-116-1171-g002.jpg

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本文引用的文献

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YAP signaling orchestrates the endothelin-1-guided invadopodia formation in high-grade serous ovarian cancer.YAP 信号协调内皮素-1 指导的高级别浆液性卵巢癌侵袭伪足形成。
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Spatially Resolved Niche and Tumor Microenvironmental Alterations in Gastric Cancer Peritoneal Metastases.胃癌腹膜转移肿瘤微环境和龛位的空间分辨改变
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Hypoxia-induced LAMB2-enriched extracellular vesicles promote peritoneal metastasis in gastric cancer via the ROCK1-CAV1-Rab11 axis.
缺氧诱导的富含 LAMB2 的细胞外囊泡通过 ROCK1-CAV1-Rab11 轴促进胃癌腹膜转移。
Oncogene. 2024 Sep;43(37):2768-2780. doi: 10.1038/s41388-024-03124-y. Epub 2024 Aug 13.
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Metastasis-associated fibroblasts in peritoneal surface malignancies.腹膜表面恶性肿瘤中的转移相关成纤维细胞。
Br J Cancer. 2024 Aug;131(3):407-419. doi: 10.1038/s41416-024-02717-4. Epub 2024 May 23.
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Tumor-associated fibrosis: a unique mechanism promoting ovarian cancer metastasis and peritoneal dissemination.肿瘤相关纤维化:促进卵巢癌转移和腹膜扩散的独特机制。
Cancer Metastasis Rev. 2024 Sep;43(3):1037-1053. doi: 10.1007/s10555-024-10169-8. Epub 2024 Mar 28.
6
Mesothelial cells with mesenchymal features enhance peritoneal dissemination by forming a protumorigenic microenvironment.具有间充质特征的间皮细胞通过形成促肿瘤微环境增强腹膜扩散。
Cell Rep. 2024 Jan 23;43(1):113613. doi: 10.1016/j.celrep.2023.113613. Epub 2024 Jan 16.
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The molecular biology of peritoneal metastatic disease.腹膜转移疾病的分子生物学。
EMBO Mol Med. 2023 Mar 8;15(3):e15914. doi: 10.15252/emmm.202215914. Epub 2023 Jan 26.
8
Immunohistochemical Markers of the Epithelial-to-Mesenchymal Transition (EMT) Are Related to Extensive Lymph Nodal Spread, Peritoneal Dissemination, and Poor Prognosis in the Microsatellite-Stable Diffuse Histotype of Gastric Cancer.上皮-间质转化(EMT)的免疫组织化学标志物与微卫星稳定型弥漫性组织学类型胃癌的广泛淋巴结转移、腹膜播散及不良预后相关。
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