ALCAM/CD166: A pleiotropic mediator of cell adhesion, stemness and cancer progression

Cytokine Growth Factor Rev. 2021 Oct:61:27-37. doi: 10.1016/j.cytogfr.2021.07.001. Epub 2021 Jul 9.

Abstract

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) is a glycoprotein involved in homotypic and heterotypic cell adhesion. ALCAM can be proteolytically cleaved at the cell surface by metalloproteases, which generate shedding of its ectodomain. In various tumors, ALCAM is overexpressed and serves as a valuable prognostic marker of disease progression. Moreover, CD166 has been identified as a putative cancer stem cell marker in particular cancers. Herein, we summarize biochemical aspects of ALCAM, including structure, proteolytic shedding, alternative splicing, and specific ligands, and integrate this information with biological functions of this glycoprotein including cell adhesion, migration and invasion. In addition, we discuss different patterns of ALCAM expression in distinct tumor types and its contribution to tumor progression. Finally, we highlight the role of ALCAM as a cancer stem cell marker and introduce current clinical trials associated with this molecule. Future studies are needed to define the value of shed ALCAM in biofluids or ALCAM isoform expression as prognostic biomarkers in tumor progression.

Keywords: ALCAM/CD166; Cancer stem cell marker; Shedding; Structure; Tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule*
  • Antigens, CD
  • Biomarkers, Tumor
  • Cell Adhesion
  • Cell Adhesion Molecules, Neuronal
  • Fetal Proteins
  • Humans
  • Neoplasms*
  • Neoplastic Stem Cells

Substances

  • ALCAM protein, human
  • Activated-Leukocyte Cell Adhesion Molecule
  • Antigens, CD
  • Biomarkers, Tumor
  • Cell Adhesion Molecules, Neuronal
  • Fetal Proteins