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Introduction
Currently, cancer is one of most common causes of mortality worldwide. Colorectal cancer (CRC) represents one of the most frequently diagnosed cancer types and is the fourth leading cause of cancer-related death (1). The spreading of cells from the primary lesion to a secondary organ and the subsequent development of distant metastases is a key factor that limits patient survival rate. This remains one of the most complex issues faced in medicine (2).
The liver is the main target organ for metastatic CRC cells and the second most commonly invaded organ, after the lymph nodes (3). In fact, 15–25% of CRC patients present with synchronous hepatic metastases at the time of diagnosis, and a further 30% will later develop liver metastasis (4,5). The complex network of vessels and microcapillaries of the hepatic microcirculation makes the liver a target for circulating cells (6). Indeed, cancer cells released from a primary lesion follow a natural blood flow directly to the liver, through the specialized microvessel network known as the liver sinusoids. Gastric cancers also commonly metastasize to the liver (7). Circulating cells from other primary malignancies, such as melanoma, breast or neuroendocrine tumors (8–10), also adhere, establish and develop in the liver, giving rise to metastases, although this is less common.
Metastatic progression is a highly complex and coordinated cascade of events that is influenced by a wide variety of mediators (11,12). Among the key factors that participate in this process, adhesion molecules expressed on cancer cells and cells of the target organ have a crucial role (13,14). Adhesion molecules generate the initial cell-cell contacts that lead to cancer cell extravasation and organ colonization. Additionally, these proteins may also act as signaling molecules to modulate the local microenvironment, creating a pro-metastatic environment, and trigger an angiogenic and desmoplastic response via a complex reciprocal dialogue between the tumor cells and the cells of the colonized organ (15,16). In addition to the tissue cells, immune populations recruited from the circulation during metastasis formation are also involved in generating a favorable environment for metastatic growth (17,18). Therefore, determining the role of adhesion molecules during the different stages of this process remains a major goal for our understanding of the metastatic cascade. This, in turn, will facilitate new opportunities...