Activated leukocyte cell adhesion molecule (ALCAM), also known as CD166, is a cell adhesion protein that is found in multiple cell types. ALCAM has multiple and diverse roles in various physiological and pathological conditions, including inflammation and cancer. There has been compelling evidence of ALCAM’s prognostic value in solid cancers, indicating that it is a potential therapeutic target. The present article overviews the recent findings and progress in ALCAM and its involvement in cancer, with a primary focus on its clinical connections in cancer and therapeutic values.

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is a cell–cell adhesion protein conferring heterotypic and homotypic interactions between cells of the same type and different types. It is aberrantly expressed in various cancer types and has been shown to be a regulator of cancer metastasis. In the present study, we investigated potential roles of ALCAM in the peritoneal transcoelomic metastasis in gastrointestinal cancers, a metastatic type commonly occurred in gastro-intestinal and gynaecological malignancies and resulting in poor clinical outcomes. Specifically, we studied whether ALCAM acts as both a ‘seed’ receptor in these tumour cells and a ‘soil’ receptor in peritoneal mesothelial cells during cancer metastasis. Gastric cancer and pancreatic cancer tissues with or without peritoneal metastasis were compared for their levels of ALCAM expression. The impact of ALCAM expression in these tumours was also correlated to the patients’ clinical outcomes, namely peritoneal metastasis-free survival. In addition, cancer cells of gastric and pancreatic origins were used to create cell models with decreased or increased levels of ALCAM expression by genetic knocking down or overexpression, respectively. Human peritoneal mesothelial cells were also genetically transfected to generate cell models with different profiles of ALCAM expression. These cell models were used in the tumour-mesothelial interaction assay to assess if and how the interaction was influenced by ALCAM. Both gastric and pancreatic tumour tissues from patients who developed peritoneal metastases had higher levels of ALCAM transcript than those without. Patients who had tumours with high levels of ALCAM had a much shorter peritoneal metastasis free survival compared with those who had low ALCAM expression (p = 0.006). ALCAM knockdown of the mesothelial cell line MET5A rendered the cells with reduced interaction with both gastric cancer cells and pancreatic cancer cells. Likewise, levels of ALCAM in both human gastric and pancreatic cancer cells were also a determining factor for their adhesiveness to mesothelial cells, a process that was likely to be triggered the phosphorylation of the SRC kinase. A soluble ALCAM (sALCAM) was found to be able to inhibit the adhesiveness between cancer cells and mesothelial cells, mechanistically behaving like a SRC kinase inhibitor. ALCAM is an indicator of peritoneal metastasis in both gastric and pancreatic cancer patients. It acts as not only a potential peritoneal ‘soil’ receptor of tumour seeding but also a ‘soil’ receptor in peritoneal mesothelial cells during cancer metastasis. These findings have an important therapeutic implication for treating peritoneal transcoelomic metastases.

Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a cell adhesion molecule and one of the potential metastasis ‘soil’ receptors that via homotypic and heterotypic interactions, mediates cell adhesion. The present study investigated the clinical, pathological and prognostic value of ALCAM in patients with pancreatic cancer. Pancreatic cancer tissues (n = 223), collected immediately after surgery, were analysed for levels of the ALCAM transcripts. The expression was analysed against clinical, pathological and clinical outcome of the patients. We validated our findings with an available TCGA database (n = 117), including correlations with the ALCAM interactive partners. Pancreatic cancer tissues had significantly higher levels of ALCAM transcript than normal tissues (P < 0.00001). There were no significant differences with staging, differentiation and tumour locations. Tumours from patients who died of pancreatic cancer had significantly high levels of ALCAM compared with those who lived (P = 0.018), finding also supported by ROC analysis (P = 0.016). Multivariant analysis showed ALCAM as an independent prognosis factor for overall survival (hazardous ratio 5.485), with both nodal status and TNM staging contributing to the model (HR 2.578 and 3.02 respectively). A surprising finding was the relationship between ALCAM expression and microvessel embolism of tumour cells (P = 0.021, with vs without tumour embolism). ALCAM significantly correlated with its interactive protein partners including CD6 and ITGB1, but not L1CAM. ALCAM/CD166 expression is aberrant in pancreatic cancer and the raised expression is an independent prognostic factor for the survival of the patients and the microvessel embolism by cancer cells. ALCAM is a prognostic indicator for survival and tumour embolism in pancreatic cancer

ALCAM (also known as CD166) is a membrane integral protein and said to have a role in predicting the clinical outcome of patients with breast cancer, but the pattern of the prediction value is inconsistent. ALCAM confers cell-cell adhesion via heterotypic and homotypic interactions and linked to cytoskeleton via the ERM protein family (Ezrin, Moesin, Radixin and EHM2), particularly ezrin. The present study explored if the ALCAM and its ERM linkers may assist in refining the prognostic value of ALCAM. Gene transcripts of ACLAM and the ERM family members were quantitatively analysed in an existing breast cancer cohort collected freshly after surgery. The relationship between ALCAM and patient’s survival (follow-up 10 years) were stratified by the ALCAM linkers. Statistical methods were Kaplan-Meier’s survival method, ROC and logistic regression. ALCAM significantly correlated with four ERM family members (P < 0.005). Patients with high levels of ALCAM transcripts had significantly long overall survival. Further stratification by the epithelial rich Ezrin and endothelial rich Moesin identified subgroup of patients with good prognosis. Multivariant analysis indicates that the combined power of ALCAM and ERM family serves as an independent prognostic factor (P = 0.003) together with the other two factors, namely the Nottingham Prognostic Index and Nodal status (P = 0.02). A similar prediction power for disease free survival was seen with ALCAM and ERM combination. ALCAM and its intracellular cytoskeletal linker molecules, the ERM family, together forms a significant prognostic factor to the clinical outcome of patients with breast cancer. ALCAM stratified by the ERM family have prognostic value in breast cancer