Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Columbus, OH 43210, USA.
Department of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Cells. 2023 Jun 18;12(12):1657. doi: 10.3390/cells12121657.
The liver is the most frequently target for metastasis among patients with colorectal cancer mainly because of the portal vein circulation that directly connects the colon and rectum with the liver. The liver tumor microenvironment consists of different cell types each with unique characteristics and functions that modulate the antigen recognition and immune system activation. Primary tumors from other sites "prime" the liver prior to the seeding of cancer cells, creating a pre-metastatic niche. Following invasion into the liver, four different phases are key to the development of liver metastases: a microvascular phase in which cancer cells infiltrate and become trapped in sinusoidal vessels; an extravascular, pre-angiogenic phase; an angiogenic phase that supplies oxygen and nutrients to cancer cells; and a growth phase in which metastatic cells multiply and enlarge to form detectable tumors. Exosomes carry proteins, lipids, as well as genetic information that can create a pre-metastatic niche in distant sites, including the liver. The complexity of angiogenic mechanisms and the exploitation of the vasculature in situ by cancer cells have limited the efficacy of currently available anti-angiogenic therapies. Delineating the molecular mechanisms implicated in colorectal liver metastases is crucial to understand and predict tumor progression; the development of distant metastases; and resistance to chemotherapy, immunotherapy, and targeted treatment.
肝脏是结直肠癌患者转移的最常见靶器官，主要是因为门静脉循环直接将结肠和直肠与肝脏连接。肝脏肿瘤微环境由不同的细胞类型组成，每种细胞类型都具有独特的特征和功能，调节抗原识别和免疫系统激活。来自其他部位的原发性肿瘤在癌细胞播种前“启动”肝脏，形成预先转移的生态位。癌细胞侵入肝脏后，四个不同的阶段是肝脏转移发展的关键：癌细胞浸润并被困在窦状血管中的微血管阶段；血管外、血管前期；为癌细胞提供氧气和营养的血管生成阶段；以及转移性细胞增殖和增大形成可检测肿瘤的生长阶段。外泌体携带蛋白质、脂质以及遗传信息，可以在远处部位（包括肝脏）形成预先转移的生态位。血管生成机制的复杂性以及癌细胞对原位血管的利用限制了现有抗血管生成疗法的疗效。阐明结直肠癌肝转移涉及的分子机制对于理解和预测肿瘤进展、远处转移的发展以及对化疗、免疫疗法和靶向治疗的耐药性至关重要。
