Liver Metastasis-Related Genes at Primary and Metastatic Sites from Patients with Colon Cancer

Colorectal cancer (CRC) frequently metastasizes to the liver, but the genetic and phenotypic properties of specific cancer cells able to implant and grow in this organ have not yet been established. Neither is it known the contribution of the patient’s genetic, physiologic and pathologic backgrounds to hepatic CRC metastasis. DNA microarray and RT-PCR were first used to determine hepatic metastasis signature genes in biopsies from primary and metastatic CRCs. Our results showed that hepatic metastasis occurrence was in part associated with marked gene expression changes that originated in the primary CRC tumors. However, other CRC gene changes were liver-dependent and were regulated by hepatic parenchymal and non-parenchymal cells, which represent the new microenvironment for metastatic CRC cancer cells. Conversely, several prometastatic genes were also induced in the liver by both CRC-derived soluble factors and systemic factors from the patient, suggesting that the hepatic metastasis microenvironment is acting as a functional interconnector between liver pathophysiology and metastatic cell biology in patients with CRC. Next, new surgical biopsies were obtained from early and advanced stage CRC patients, and TaqMan-low density arrays were used to quantify prometastatic gene expression level at primary/metastatic sites and the liver from CRC patients with and without metastases. We verified that together with metastasis-related gene profiles, which suggested the existence of a prometastatic potential in primary tumors, other signature genes, representing the pro-metastatic microenvironment supported by the liver reaction to CRC factors, were also detected in liver biopsies from patients with no liver metastases, suggesting their potential for individual assessment of hepatic metastasis risk in CRC patients. Knowledge on hepatic metastasis genes and their regulation by the hepatic microenvironment open new opportunities for therapeutic intervention during CRC metastasis.