Blocking alpha2 integrins on rat CC531s colon carcinoma cells prevents operation-induced augmentation of liver metastases outgrowth.
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.


CONCLUSIONS
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.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D005434:Flow Cytometry; D039421:Integrin alpha2 / Q000276:immunology*; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D018613:Microscopy, Confocal; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D051381:Rats
D000911:Antibodies, Monoclonal; D039421:Integrin alpha2