ALCAM/CD166: Cancer-related Issues

Cancer Genomics - Proteomics

DANIELA EGGLE¹  GUIDO W.M. SWART²  ULRICH H. WEIDLE¹  STEFAN KLOSTERMANN¹ 

[1] Roche Diagnostics GmbH, Pharma Division, D-82372 Penzberg, GermanyRoche Diagnostics GmbH, Pharma Division, D-82372 Penzberg, GermanyRoche Diagnostics GmbH, Pharma Division, D-82372 Penzberg, Germany;Educational Institute WiNST, Faculty of Science, Radboud University Nijmegen, NL-6500 GL Nijmegen, the NetherlandsEducational Institute WiNST, Faculty of Science, Radboud University Nijmegen, NL-6500 GL Nijmegen, the NetherlandsEducational Institute WiNST, Faculty of Science, Radboud University Nijmegen, NL-6500 GL Nijmegen, the Netherlands

关键词: Adhesion and aggregation;    dissemination and metastasis;    homo- and heterophilic interactions;    malignant melanoma;    prognostic marker;    target validation;    therapeutic intervention;    review;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

Activated leucocyte adhesion molecule (ALCAM) was originally identified as a transmembrane receptor which is involved in T-cell activation and has other still unresolved functions in hematopoiesis, development, inflammation and transendothelial migration of neutrophils. ALCAM is a member of a subfamily of immunoglobulin receptors with five immunoglobulin-like domains (VVC2C2C2) in the extracellular domain and is expressed in many types of tumors. The tumor-type-dependent impact of its expression level with respect to prognosis points to a possible context-dependent function. Most functional investigations have focused on malignant melanoma, in which high ALCAM expression at the protein level correlates with a poor prognosis. ALCAM mediates low-affinity homophilic interactions and much stronger interactions with CD6. Modulation of ALCAM function with agents such as transfected dominant negative ALCAM and ligand-binding secreted ALCAM both lead to inhibition of matrix metalloproteinase-2 activation, but their impact with respect to invasion in vitro and metastasis in vivo are different. Single-chain Fv fragments directed against ALCAM are efficiently internalized, paving the way for exploration of immunoconjugates as therapeutic agents. Validation experiments of the target with modulatory agents for possible therapeutic application in oncology are discussed.

【 授权许可】

Unknown