Giordano Marco, Cavallaro Ugo
Unit of Gynaecological Oncology Research, European Institute of Oncology IRCSS, 20128 Milan, Italy.
J Clin Med. 2020 May 16;9(5):1502. doi: 10.3390/jcm9051502.
L1 cell adhesion molecule (L1CAM) is aberrantly expressed in several tumor types where it is causally linked to malignancy and therapy resistance, acting also as a poor prognosis factor. Accordingly, several approaches have been developed to interfere with L1CAM function or to deliver cytotoxic agents to L1CAM-expressing tumors. Metastatic dissemination, tumor relapse and drug resistance can be fueled by a subpopulation of neoplastic cells endowed with peculiar biological properties that include self-renewal, efficient DNA repair, drug efflux machineries, quiescence, and immune evasion. These cells, known as cancer stem cells (CSC) or tumor-initiating cells, represent, therefore, an ideal target for tumor eradication. However, the molecular and functional traits of CSC have been unveiled only to a limited extent. In this context, it appears that L1CAM is expressed in the CSC compartment of certain tumors, where it plays a causal role in stemness itself and/or in biological processes intimately associated with CSC (e.g., epithelial-mesenchymal transition (EMT) and chemoresistance). This review summarizes the role of L1CAM in cancer focusing on its functional contribution to CSC pathophysiology. We also discuss the clinical usefulness of therapeutic strategies aimed at targeting L1CAM in the context of anti-CSC treatments.
L1细胞粘附分子（L1CAM）在多种肿瘤类型中异常表达，与恶性肿瘤和治疗耐药性存在因果关系，也是预后不良的因素。因此，人们已开发出多种方法来干扰L1CAM的功能，或向表达L1CAM的肿瘤递送细胞毒性药物。具有自我更新、高效DNA修复、药物外排机制、静止和免疫逃逸等特殊生物学特性的肿瘤细胞亚群可促进转移扩散、肿瘤复发和耐药。这些细胞被称为癌症干细胞（CSC）或肿瘤起始细胞，因此是肿瘤根除的理想靶点。然而，CSC的分子和功能特性仅在有限程度上得到揭示。在这种情况下，L1CAM似乎在某些肿瘤的CSC区室中表达，在干性本身和/或与CSC密切相关的生物学过程（如上皮-间质转化（EMT）和化疗耐药）中发挥因果作用。本综述总结了L1CAM在癌症中的作用，重点关注其对CSC病理生理学的功能贡献。我们还讨论了在抗CSC治疗背景下靶向L1CAM的治疗策略的临床实用性。
