L1CAM Specific Neutra™ Antibody Products

The L1 cell adhesion molecule (L1CAM) is a transmembrane protein member of the immunoglobulin superfamily. It is encoded by the L1CAMgene on the X chromosome. L1CAM is widely expressed in various tissues, including the nervous system, kidneys, and epithelial tissues, and its expression is particularly prominent during embryonic development. It comprises an extracellular domain with six immunoglobulin-like domains and five fibronectin type III repeats, a transmembrane domain, and a cytoplasmic tail. As a neuronal cell adhesion molecule, L1CAM is involved in neuronal migration, synaptic development and axon guidance. The dysfunction of L1CAM is associated with neurological disorders such as X-linked hydrocephalus and corpus callosum agenesis.

Its Gene ID: 6470, UniProtKB ID: P32004, and OMIM ID: 308840.

L1CAM Signaling Pathways

L1CAM can induce the endocytosis of integrin β-1 by interfering with integrin-related signaling pathways, thereby enhancing cell motility. Expression of L1CAM can also activate the ERK pathway and induce NFκB, β3 integrin subunit, and small GTPase activities, thereby increasing cell viability and invasion ability. L1CAM can interact with various molecules in cis or trans, including other neural cell adhesion molecules, integrins, and β catenin-Wnt signaling molecules. In addition, the cytoplasmic tail of L1CAM can interact with cytoskeletal proteins such as ankyrin, actin, spectrin, and Ezrin. These interactions control L1CAM expression on the membrane through endocytosis, mediate interactions with the cytoskeleton, and activate downstream signaling pathways.

Fig.1 Full-length L1CAM signaling pathways in the plasma membrane and their role in cancer progression-associated events.¹

L1CAM in Cancer

L1CAM plays a role in cancer by affecting different signaling pathways that conceivably contribute to tumor progression. Expression of L1CAM confers higher growth rate, increased cell motility, cell transformation, and enhanced tumorigenic capacities in colon cancer cells. The interaction between soluble L1CAM and neuropilin-1 may contribute to the growth of ovarian carcinomas and reciprocal signaling between mesothelial cells and tumors. Besides, it is found that ovarian carcinoma cells expressing L1CAM are more resistant to apoptosis. IHC analysis revealed expression of L1CAM in 80% of pancreatic adenocarcinomas. Studies have also shown that expression of L1CAM in breast cancer cells triggers a phenomenon like EMT, that is, disruption of adherens junctions, downregulation of E-cadherin expression in the junctions, and subsequent increase in b-catenin transcriptional activity. In addition, L1CAM expression is also observed in both low metastatic and high metastatic melanoma cells, and several other neuronal tumors including Schwannoma and glioma.

Antibodies Targeting L1CAM

The expression of L1CAM in a wide variety of human cancers makes it a possible useful marker in the diagnosis of patients with advanced stages of cancer, and a potential candidate for therapeutic intervention. Moreover, since L1CAM is implicated in almost every aspect of cancer progression, targeting L1CAM could interfere with tumor progression. Antibodies against L1CAM have been previously shown to have therapeutic potential since they can inhibit cancer cell proliferation, migration, and tumor growth in vitro. In In vivo experiments, anti-L1CAM antibody treatment can suppress the intra-peritoneal growth of ovarian carcinoma cells, as well as tumor formation and tumor invasion of other tumors. Monoclonal antibodies against L1CAM can inhibit the signaling pathways activated by L1CAM, such as preventing the activation of Src and Erk and the expression of target genes induced by Erk, thus affecting invasion and proliferation.

Fig.2 Neutralizing antibodies targeting L1CAM for cancer treatment.²

Creative Biolabs offers different kinds of high-quality anti-L1CAM antibody products that could be used in six applications.

REFERENCES

1. van der Maten, Miriam, et al. "L1 cell adhesion molecule in cancer, a systematic review on domain-specific functions." International journal of molecular sciences 20.17 (2019): 4180. Distributed under Open Access license CC BY 4.0. The image was modified by extracting and using only part of the original image.
2. Giordano, Marco, and Ugo Cavallaro. "Different shades of L1CAM in the pathophysiology of cancer stem cells." Journal of clinical medicine 9.5 (2020): 1502. Distributed under Open Access license CC BY 4.0, without modification.