The Liver Prometastatic Reaction of Cancer Patients: Implications for Microenvironment-Dependent Colon Cancer Gene Regulation

Abstract

Colon cancer 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. The contribution of the patient's genetic, physiologic and pathologic backgrounds to the incidence and development of hepatic colon cancer metastases is also presently misunderstood. At a transcriptional level, hepatic metastasis development is in part associated with marked changes in gene expression of colon cancer cells that may originate in the primary tumor. Other changes occur in the liver and are regulated by hepatic cells, which represent the new microenvironment for metastatic colon cancer cells. However, hepatic parenchymal and non-parenchymal cell functions are also affected by both tumor-derived factors and systemic host factors, which suggests that the hepatic metastasis microenvironment is a functional linkage between the hepatic pathophysiology of the colon cancer patient and the biology of its cancer cells. Therefore, together with metastasis-related gene profiles suggesting the existence of liver metastasis potential in primary tumors, new biomarkers of the prometastatic microenvironment supported by the liver reaction to colon cancer factors may be helpful for the individual assessment of hepatic metastasis risk in colon cancer patients. In addition, knowledge on hepatic metastasis gene regulation by the hepatic microenvironment may open multiple opportunities for therapeutic intervention during colon cancer metastasis at both subclinical and advanced stages.

Capture of Viable Circulating Tumor Cells in the Liver of Colorectal Cancer Patients

“…Interestingly, the liver architecture and complex functions may explain the implication of this organ for CRC metastasis (30 ). Different liver-specific elements constitute a functional microenvironment representing the microenvironment encountered by circulating colon cancer cells entering the liver as described by .…”

“…Moreover, the prognostic relevance of these assays including the Epispot applied in this study needs to be examined on large cohorts of CRC patients. A specific microenvironment-related colon cancer gene signature in the liver was identified, as well as genes representing the liver prometastatic reaction, but their specific roles in the pathogenesis of hepatic metastasis is still under investigation (30 ). Future investigations should focus on defining the best markers of the subpopulation of functional CTCs that are the metastasisinitiating cells, defining the role of EpCAM in liver metastases formation, and identifying factors from colon CTCs able to induce the prometastatic microenvironment of the liver.…”

Silencing of sinusoidal DDR1 reduces murine liver metastasis by colon carcinoma

“…The liver is the most common site for colorectal carcinoma (CRC) metastasis. Successful arrest and growth of tumor cells occurs within the sinusoidal vessels 26 . The collagen deposition observed afterward induces cancer stiffness that enhances tumor growth and metastatic colonization 27 .…”

Colorectal Cancer Metastases Settle in the Hepatic Microenvironment Through α5β1 Integrin

“…The microenvironment surrounding cancer cells acts as a functional entity inducing and responding to tumour and host factors [Schedin and Keely, ; Vidal‐Vanaclocha, ], and determining the colonization of invasive cells in particularly favourite organs [Weiss, ; Friedl and Wolf, ].…”