Morabito Marika, Thibodot Pauline, Gigandet Anthony, Compagnon Philippe, Toso Christian, Berishvili Ekaterine, Lacotte Stéphanie, Peloso Andrea
General, Emergency and Transplant Surgery Department, ASST Settelaghi, University Hospital and Faculty of Medicine of Insubria, 21100 Varese, Italy.
Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique-Hôpitaux de Paris, 94800 Villejuif, France.
Cancers (Basel). 2025 Mar 12;17(6):953. doi: 10.3390/cancers17060953.
The liver is the most common site of metastasis of colorectal cancer (CRC), and colorectal liver metastasis is one of the major causes of CRC-related deaths worldwide. The tumor microenvironment, particularly the extracellular matrix (ECM), plays a critical role in CRC metastasis and chemoresistance. Based on findings from clinical and basic research, this review attempts to offer a complete understanding of the role of the ECM in colorectal liver metastasis and to suggest potential ways for therapeutic intervention. First, the ECMs' role in regulating cancer cell fate is explored. We then discuss the hepatic ECM fingerprint and its influence on the metastatic behavior of CRC cells, highlighting key molecular interactions that promote metastasis. In addition, we examine how changes in the ECM within the metastatic niche contribute to chemoresistance, focusing on ECM remodeling by ECM stiffening and the activation of specific signaling pathways. Understanding these mechanisms is crucial for the development of novel strategies to overcome metastasis and improve outcomes for CRC patients.
肝脏是结直肠癌（CRC）最常见的转移部位，结直肠癌肝转移是全球CRC相关死亡的主要原因之一。肿瘤微环境，尤其是细胞外基质（ECM），在CRC转移和化疗耐药中起关键作用。基于临床和基础研究的结果，本综述试图全面了解ECM在结直肠癌肝转移中的作用，并提出潜在的治疗干预方法。首先，探讨ECM在调节癌细胞命运中的作用。然后，我们讨论肝脏ECM指纹及其对CRC细胞转移行为的影响，突出促进转移的关键分子相互作用。此外，我们研究转移微环境中ECM的变化如何导致化疗耐药，重点关注ECM硬化和特定信号通路激活引起的ECM重塑。了解这些机制对于开发克服转移的新策略和改善CRC患者的预后至关重要。
