Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Química Biológica, Buenos Aires, Argentina; CONICET-Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) Prof. Alejandro C. Paladini, Buenos Aires, Argentina.
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina; Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Cytokine Growth Factor Rev. 2021 Oct;61:27-37. doi: 10.1016/j.cytogfr.2021.07.001. Epub 2021 Jul 9.
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.
激活白细胞细胞黏附分子（ALCAM/CD166）是一种参与同质和异质细胞黏附的糖蛋白。ALCAM 可以在细胞表面被金属蛋白酶进行蛋白水解切割，从而产生其细胞外结构域的脱落。在各种肿瘤中，ALCAM 过表达，并作为疾病进展的有价值的预后标志物。此外，CD166 已被确定为某些癌症中的推定癌症干细胞标志物。在此，我们总结了 ALCAM 的生化方面，包括结构、蛋白水解脱落、选择性剪接和特定配体，并将这些信息与该糖蛋白的生物学功能整合在一起，包括细胞黏附、迁移和侵袭。此外，我们讨论了不同肿瘤类型中 ALCAM 的不同表达模式及其对肿瘤进展的贡献。最后，我们强调了 ALCAM 作为癌症干细胞标志物的作用，并介绍了与该分子相关的当前临床试验。未来的研究需要确定脱落的 ALCAM 在生物流体中的价值，或作为肿瘤进展中预后生物标志物的 ALCAM 同工型表达。
