L1CAM in the Early Enteric and Urogenital System

Abstract

Article IntroductionIn 1984, Rathjen and Schachner identified a new cell adhesion molecule (L1 cell adhesion molecule [L1CAM]) in neurons that turned out to be a key player in the neuronal development of mice where it governs neuronal outgrowth, migration, and axonal guidance. 1 L1CAM is a transmembrane protein belonging to the immunoglobulin superfamily, interacting with several ligands such as integrins, neuropilins, contactin 1 and 2, CD24, as well as with its shed form. 2Apart from its established function, studies in rodents and cell lines showed that L1CAM has an essential role in the formation and maintenance of epithelia, which is achieved via two contrary modes of action: On the one hand, L1CAM is important for both the establishment of cell-cell complexes and the SummaryL1 cell adhesion molecule (L1CAM) is a transmembrane molecule belonging to the L1 protein family. It has shown to be a key player in axonal guidance in the course of neuronal development. Furthermore, L1CAM is also crucial for the establishment of the enteric and urogenital organs and is aberrantly expressed in cancer originating in these organs. Carcinogenesis and embryogenesis follow a lot of similar molecular pathways, but unfortunately, comprehensive data on L1CAM expression and localization in human developing organs are lacking so far. In the present study we, therefore, examined the spatiotemporal distribution of L1CAM in the early human fetal period (weeks 8-12 of gestation) by means of immunohistochemistry and in situ hybridization (ISH). In the epithelia of the gastrointestinal organs, L1CAM localization cannot be observed in the examined stages most likely due to their advanced polarization and differentiation. Despite these results, our ISH data indicate weak L1CAM expression, but only in few epithelial cells. The genital tracts, however, are distinctly L1CAM positive throughout the entire fetal period. We, therefore, conclude that in embryogenesis L1CAM is crucial for further differentiation of epithelia. (J Histochem Cytochem 65:21-32, 2017)

TGF-β1 secreted by pancreatic stellate cells promotes stemness and tumourigenicity in pancreatic cancer cells through L1CAM downregulation

“…The pancreatic stellate cells (PSC) within the tumour microenvironment represent the principal source of TGF-β1 [7,8], but still very little is known about the TGF-β1-mediated crosstalk between PSC and PDAC cells. While L1 cell adhesion molecule (L1CAM; CD171) was originally discovered in the nervous system due to its important function for axon guidance and cell migration [9][10][11][12][13][14][15], it has also been shown to be a crucial factor for tumour cell dissemination and metastasis in colorectal, breast, kidney and lung cancer [16,17]. In PDAC, the expression of L1CAM could only be detected in 2 out of 111 patients (2%), whereas 98% of the samples were reportedly L1-negative [18].…”

Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies

“…L1CAM is a transmembrane protein belonging to the immunoglobulin superfamily that interacts with several ligands, such as integrins, neuropilins, contactin 1 and 2, and CD24, as well as with the shed form [ 24 ]. In disease-free adults, L1CAM was observed exclusively in kidney epithelia [ 25 ]. Although we cannot rule out that the EXs are secreted by maternal neurons, EXs still contain fetal neurons.…”

Dendrites with specialized glial attachments develop by retrograde extension using SAX-7 and GRDN-1

“…How loss of L1CAM leads to such a broad spectrum of phenotypes remains mysterious. Interestingly, L1CAM is also expressed in some epithelial tissues, but less is known about its roles in this context (Debiec et al, 1998;Nolte et al, 1999;Pechriggl et al, 2017).…”