van der Bij Gerben J, Oosterling Steven J, Bögels Marijn, Bhoelan Farien, Fluitsma Donna M, Beelen Robert H J, Meijer Sybren, van Egmond Marjolein
Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Hepatology. 2008 Feb;47(2):532-43. doi: 10.1002/hep.22013.
Currently, an operation is the only curative option for patients with colorectal cancer. Unfortunately, many patients will develop liver metastases even after successful resection of the primary tumor. Removal of primary colorectal carcinoma may paradoxically increase the risk of metastases development, because accumulating evidence suggests that surgical trauma can stimulate tumor growth. In the present study, we investigated the effects of abdominal trauma on liver metastases development. Surgical trauma dramatically increased adhesion of tumor cells in the liver, leading to enhanced outgrowth of metastases. Endothelial stress was observed rapidly after an operation, suggesting that abdominal trauma resulted in impairment of blood vessel integrity. Tumor cells preferentially adhered to extracellular matrix (ECM). Furthermore, preincubation of tumor cells with anti-alpha2 integrin antibodies completely reverted operation-induced augmentation of CC531s adhesion and liver metastases outgrowth. As such, we postulate that blood vessel integrity in the liver is compromised after abdominal trauma, resulting in enhanced ECM exposure, which enables tumor cell adhesion and metastases outgrowth.
Perioperative treatments that either aim to reduce endothelial stress or block the interaction between tumor cells and ECM represent promising new therapeutic strategies for the prevention of liver metastases development after resection of the primary tumor.
目前，手术是结直肠癌患者唯一的治愈选择。不幸的是，许多患者即使在成功切除原发肿瘤后仍会发生肝转移。切除原发性结直肠癌可能反常地增加转移发生的风险，因为越来越多的证据表明手术创伤会刺激肿瘤生长。在本研究中，我们调查了腹部创伤对肝转移发生的影响。手术创伤显著增加了肿瘤细胞在肝脏中的黏附，导致转移灶生长增强。术后很快观察到内皮应激，提示腹部创伤导致血管完整性受损。肿瘤细胞优先黏附于细胞外基质（ECM）。此外，用抗α2整合素抗体预孵育肿瘤细胞可完全逆转手术诱导的CC531s黏附增强和肝转移灶生长。因此，我们推测腹部创伤后肝脏血管完整性受损，导致ECM暴露增加，这使得肿瘤细胞黏附并促进转移灶生长。
旨在减轻内皮应激或阻断肿瘤细胞与ECM之间相互作用的围手术期治疗是预防原发性肿瘤切除后肝转移发生的有前景的新治疗策略。
