Role Of Neural Cell Adhesion Molecule Research Articles

Ubiquitous Neural Cell Adhesion Molecule (NCAM): Potential Mechanism and Valorisation in Cancer Pathophysiology, Drug Targeting and Molecular Transductions.

Neural cell adhesion molecule, an integrated molecule of immunoglobulin protein superfamily involved in cell-cell adhesion, undergoes various structural modifications through numerous temporal-spatial regulations that generously alter their expressions on cell surfaces. These varied expression patterns are mostly envisioned in the morphogenesis and innervations of different human organs and systems. The considerable role of NCAM in neurite growth, brain development and etc. and its altered expression of NCAM in proliferating tumour cells and metastasis of various human melanomas clearly substantiate its appropriateness as a cell surface marker for diagnosis and potential target for several therapeutic moieties. This characteristic behaviour of NCAM is confined to its novel biochemistry, structural properties, signalling interactions and polysialylation. In particular, the characteristic expressions of NCAM are mainly attributed by its polysialylation, a post-translational modification that attaches polysialyl groups to the NCAM. The altered expression of NCAM on cell surface develops curiosity amidst pharmaceutical scientists, which drives them to understand its role of such expressions in various human melanomas and to elucidate the promising therapeutic strategies that are currently available to target NCAM appositely. Therefore, this review article is articulated with an insight on the altered expressions of NCAM, the clinical significances and the consequences of such atypical expression patterns in various human organs and systems.

Decreased Serum NCAM Levels Associated with Cognitive Impairment in Vascular Dementia.

Objective Neural cell adhesion molecule (NCAM), a glycoprotein widely distributed in the brain, has recently been shown to regulate neuroplasticity. However, the role of NCAM in vascular dementia (VaD) is still unclear. The purpose of this study is to determine whether NCAM is involved in the course of VaD. Methods Continuous recruitment of VaD patients and control population to join this study. Doctors or nurses are responsible for collecting their clinical characteristics including age, gender, formal education, heart rate, supine systolic blood pressure, supine diastolic blood pressure, fasting glucose, high-density lipoprotein, and low-density lipoprotein. Each participant received the Montreal Cognitive Assessment (MoCA) scale after being enrolled in the group. At the same time, their peripheral blood was collected, and their serum NCAM levels were measured by enzyme-linked immunosorbent assay (ELISA). Results 98 VaD patients and 83 age- and sex-matched controls were enrolled. There was no significant statistical difference between the VaD group and the control group in terms of the comparison of clinical characteristics (p > 0.05). The MoCA score of VaD patients was significantly lower than that of the controls (27.9 ± 1.4 vs. 23.0 ± 2.1 points, p < 0.001). In addition, the circulating NCAM level of VaD patients was also significantly lower than that of controls (21.7 ± 3.8 vs. 17.6 ± 4.2 ng/mL, p < 0.001). The circulating NCAM level of VaD patients was significantly positively correlated with MoCA score (r = 0.285, p = 0.026). After adjusting for clinical characteristics, circulating NCAM levels are still an independent pathogenic factor of VaD (regression coefficient = 0.223, p = 0.034). Conclusions VaD patients have low circulating NCAM levels, which can be used as a potential predictor of VaD.

The Neural Cell Adhesion Molecule (NCAM) Promotes Clustering and Activation of EphA3 Receptors in GABAergic Interneurons to Induce Ras Homolog Gene Family, Member A (RhoA)/Rho-associated protein kinase (ROCK)-mediated Growth Cone Collapse

Establishment of a proper balance of excitatory and inhibitory connectivity is achieved during development of cortical networks and adjusted through synaptic plasticity. The neural cell adhesion molecule (NCAM) and the receptor tyrosine kinase EphA3 regulate the perisomatic synapse density of inhibitory GABAergic interneurons in the mouse frontal cortex through ephrin-A5-induced growth cone collapse. In this study, it was demonstrated that binding of NCAM and EphA3 occurred between the NCAM Ig2 domain and EphA3 cysteine-rich domain (CRD). The binding interface was further refined through molecular modeling and mutagenesis and shown to be comprised of complementary charged residues in the NCAM Ig2 domain (Arg-156 and Lys-162) and the EphA3 CRD (Glu-248 and Glu-264). Ephrin-A5 induced co-clustering of surface-bound NCAM and EphA3 in GABAergic cortical interneurons in culture. Receptor clustering was impaired by a charge reversal mutation that disrupted NCAM/EphA3 association, emphasizing the importance of the NCAM/EphA3 binding interface for cluster formation. NCAM enhanced ephrin-A5-induced EphA3 autophosphorylation and activation of RhoA GTPase, indicating a role for NCAM in activating EphA3 signaling through clustering. NCAM-mediated clustering of EphA3 was essential for ephrin-A5-induced growth cone collapse in cortical GABAergic interneurons, and RhoA and a principal effector, Rho-associated protein kinase, mediated the collapse response. This study delineates a mechanism in which NCAM promotes ephrin-A5-dependent clustering of EphA3 through interaction of the NCAM Ig2 domain and the EphA3 CRD, stimulating EphA3 autophosphorylation and RhoA signaling necessary for growth cone repulsion in GABAergic interneurons in vitro, which may extend to remodeling of axonal terminals of interneurons in vivo.

NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of esophageal cancer regulates the survival and migration of tumor-associated macrophages and cancer cells

Tumor-associated macrophages (TAMs) have important roles in the angiogenesis and tumor immunosuppression of various cancers, including esophageal squamous cell carcinomas (ESCCs). To elucidate the roles of TAMs in ESCCs, we compared the gene expression profiles between human peripheral blood monocyte-derived macrophage-like cells (Macrophage_Ls) and Macrophage_Ls stimulated with conditioned medium of the TE series human ESCC cell line (TECM) (TAM_Ls) using cDNA microarray analysis. Among the highly expressed genes in TAM_Ls, we focused on neural cell adhesion molecule (NCAM). NCAM knockdown in TAM_Ls revealed a significant decrease of migration and survival via a suppression of PI3K-Akt and fibroblast growth factor receptor 1 (FGFR1) signaling. Stimulation by TECM up-regulated the level of FGFR1 in Macrophage_Ls. Recombinant human fibroblast growth factor-2 (rhFGF-2) promoted the migration and survival of TAM_Ls and TE-cells through FGFR1 signaling. Our immunohistochemical analysis of 70 surgically resected ESCC samples revealed that the up-regulated FGF-2 in stromal cells, including macrophages, was associated with more aggressive phenotypes and a high number of infiltrating M2 macrophages. These findings may indicate a novel role of NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of ESCCs.

Variable Expression of Neural Cell Adhesion Molecule Isoforms in Renal Tissue: Possible Role in Incipient Renal Fibrosis.

Rare neural cell adhesion molecule (NCAM) positive cells have been previously described within the normal human adult kidney interstitium, speculating that they could increase in the interstitium with incipient interstitial renal fibrosis (IRF). In the present study, among 93 biopsy samples of various kidney diseases, NCAM+ interstitial cells were detected in 62.4% cases. An increased number of NCAM+ cells was significantly observed only in incipient IRF compared to normal renal tissues and advanced IRF stages (p<0.001), independently of underlying diseases (p = 0.657). All three major NCAM isoforms’ RT-PCR bands were visible either in normal or in kidneys with incipient IRF, albeit their mRNA expression levels measured by qRT-PCR were different. Applying qRT-PCR on pure NCAM+ cells population, obtained by laser capture microdissection, significant mRNA over-expression of NCAM140kD isoform was found in NCAM+ cells within incipient IRF (p = 0.004), while NCAM120kD and NCAM180kD isoforms were not changed significantly (p = 0.750; p = 0.704; respectively). Simultaneously, qRT-PCR also showed significant αSMA (p = 0.014) and SLUG (p = 0.004) mRNAs up-regulation within the NCAM+ cells of incipient IRF, as well as highly decreased matrix metalloproteinases (MMP) -2 and -9 mRNAs (p = 0.028; p = 0.036; respectively). However, using double immunofluorescence MMP-9 could still be detectable on the protein level in rare NCAM+ cells within the incipient IRF. Further characterization of NCAM+ cells by double immunofluorescent labeling revealed their association with molecules involved in fibrosis. Fibroblast growth factor receptor 1 (FGFR1) and α5β1 integrin were extensively expressed on NCAM+ cells within the incipient IRF areas, whereas human epididymis protein-4 (HE4) was found to be present in few NCAM+ cells of both normal and interstitium with incipient fibrosis. Heterogeneity of NCAM+ interstitial cells in normal and incipient IRF, concerning molecules related to fibrosis and variable expression of NCAM isoforms, could suggest diverse role of NCAM+ cells in homeostasis and in regulation of renal fibrosis in diseased kidneys.

Functional Cross-Talk Between the Cellular Prion Protein and the Neural Cell Adhesion Molecule is Critical for Neuronal Differentiation of Neural Stem/Precursor Cells

Cellular prion protein (PrP) is prominently expressed in brain, in differentiated neurons but also in neural stem/precursor cells (NPCs). The misfolding of PrP is a central event in prion diseases, yet the physiological function of PrP is insufficiently understood. Although PrP has been reported to associate with the neural cell adhesion molecule (NCAM), the consequences of concerted PrP-NCAM action in NPC physiology are unknown. Here, we generated NPCs from the subventricular zone (SVZ) of postnatal day 5 wild-type and PrP null (-/-) mice and observed that PrP is essential for proper NPC proliferation and neuronal differentiation. Moreover, we found that PrP is required for the NPC response to NCAM-induced neuronal differentiation. In the absence of PrP, NCAM not only fails to promote neuronal differentiation but also induces an accumulation of doublecortin-positive neuronal progenitors at the proliferation stage. In agreement, we noted an increase in cycling neuronal progenitors in the SVZ of PrP-/- mice compared with PrP+/+ mice, as evidenced by double labeling for the proliferation marker Ki67 and doublecortin as well as by 5-bromo-2'-deoxyuridine incorporation experiments. Additionally, fewer newly born neurons were detected in the rostral migratory stream of PrP-/- mice. Analysis of the migration of SVZ cells in microexplant cultures from wild-type and PrP-/- mice revealed no differences between genotypes or a role for NCAM in this process. Our data demonstrate that PrP plays a critical role in neuronal differentiation of NPCs and suggest that this function is, at least in part, NCAM-dependent.

Neural cell adhesion molecule, NCAM, regulates thalamocortical axon pathfinding and the organization of the cortical somatosensory representation in mouse

To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM null mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and null mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, null mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM null mutant animals. NCAM null mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in null mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex.

A novel role for neural cell adhesion molecule in modulating insulin signaling and adipocyte differentiation of mouse mesenchymal stem cells

Neural cell adhesion molecule (NCAM) has recently been found on adult stem cells, but its biological significance remains largely unknown. In this study, we used bone-marrow-derived mesenchymal stem cells (MSCs) from wild-type and NCAM knockout mice to investigate the role of NCAM in adipocyte differentiation. It was demonstrated that NCAM isoforms 180 and 140 but not NCAM-120 are expressed on almost all wild-type MSCs. Upon adipogenic induction, Ncam(-/-) MSCs exhibited a marked decrease in adipocyte differentiation compared with wild-type cells. The role of NCAM in adipocyte differentiation was also confirmed in NCAM-silenced preadipocyte 3T3-L1 cells, which also had a phenotype with reduced adipogenic potential. In addition, we found that Ncam(-/-) MSCs appeared to be insulin resistant, as shown by their impaired insulin signaling cascade, such as the activation of the insulin-IGF-1 receptor, PI3K-Akt and CREB pathways. The PI3K-Akt inhibitor, LY294002, completely blocked adipocyte differentiation of MSCs, unveiling that the reduced adipogenic potential of Ncam(-/-) MSCs is due to insulin resistance as a result of loss of NCAM function. Furthermore, insulin resistance of Ncam(-/-) MSCs was shown to be associated with induction of tumor necrosis factor α (TNF-α), a key mediator of insulin resistance. Finally, we demonstrated that re-expression of NCAM-180, but not NCAM-140, inhibits induction of TNF-α and thereby improves insulin resistance and adipogenic potential of Ncam(-/-) MSCs. Our results suggest a novel role of NCAM in promoting insulin signaling and adipocyte differentiation of adult stem cells. These findings raise the possibility of using NCAM intervention to improve insulin resistance.

The role of NCAM in auditory fear conditioning and its modulation by stress: a focus on the amygdala

Chronic stress in rodents was shown to induce structural shrinkage and functional alterations in the hippocampus that were linked to spatial memory impairments. Effects of chronic stress on the amygdala have been linked to a facilitation of fear conditioning. Although the underlying molecular mechanisms are still poorly understood, increasing evidence highlights the neural cell adhesion molecule (NCAM) as an important molecular mediator of stress-induced structural and functional alterations. In this study, we investigated whether altered NCAM expression levels in the amygdala might be related to stress-induced enhancement of auditory fear conditioning and anxiety-like behavior. In adult C57BL/6J wild-type mice, chronic unpredictable stress resulted in an isoform-specific increase of NCAM expression (NCAM-140 and NCAM-180) in the amygdala, as well as enhanced auditory fear conditioning and anxiety-like behavior. Strikingly, forebrain-specific conditional NCAM-deficient mice (NCAM-floxed mice that express the cre-recombinase under the control of the promoter of the alpha-subunit of the calcium-calmodulin-dependent protein kinase II), whose amygdala NCAM expression levels are reduced, displayed impaired auditory fear conditioning which was not altered following chronic stress exposure. Likewise, chronic stress in these conditional NCAM-deficient mice did not modify NCAM expression levels in the amygdala or hippocampus, while they showed enhanced anxiety-like behavior, questioning the involvement of NCAM in this type of behavior. Together, our results strongly support the involvement of NCAM in the amygdala in the consolidation of auditory fear conditioning and highlight increased NCAM expression in the amygdala among the mechanisms whereby stress facilitates fear conditioning processes.

The neural cell adhesion molecule is involved in the metastatic capacity in a murine model of lung cancer

Neural cell adhesion molecule (NCAM) is involved in cell growth, migration, and differentiation. Its expression and/or polysialylation appear to be deregulated in many different cancer types. We employed the lung tumor cell line LP07, syngeneic in BALB/c mice to investigate the role of NCAM in malignant progression. LP07 cells express the three main NCAM isoforms, all of them polysialylated. This cells line, pretreated with an anti-NCAM antibody and inoculated intravenously (i.v.) into syngeneic mice, developed less and smaller lung metastases. In vitro studies showed that NCAM bound antibody inhibited cell growth, mainly due to an increase in apoptosis, associated with a decrease of cyclin D1 and enhanced expression of active caspase 3 and caspase 9. Anti-NCAM-treated LP07 cells showed impairment in their ability to migrate and adhere to several extracellular matrix components. Secreted uPA activity was also reduced. NCAM-140 knocked-down by siRNA in LP07 cells pretreated or not with anti-NCAM showed an impaired metastasizing ability upon i.v. inoculation into mice. These results suggest that anti-NCAM treatment could be mimicking homophilic trans-interactions and NCAM-140 knocked-down impairs heterophilic interactions, both leading to inhibition of metastatic dissemination. The involvement of NCAM in lung tumor progression was confirmed in human NSCLC tumors. Sixty percent of the cases expressed NCAM at tumor cell level. A multivariate analysis indicated that NCAM expression was associated with a shorter overall survival in this homogeneous series of Stages I and II NSCLC patients. NCAM may be able to modulate mechanisms involved in lung carcinoma progression and represents an attractive target to control metastatic progression.

NCAM in Long-Term Potentiation and Learning

The neural cell adhesion molecule (NCAM) is important in regulating neuronal development and plasticity by modulating cell adhesion and signal transduction. Studies using NCAM antibodies have demonstrated a role of NCAM in hippocampal long-term potentiation and in animal learning models. These findings have been supported by the observation that NCAM-deficient mice show altered LTP as well as learning deficits. A particular carbohydrate modification of NCAM, polysialic acid (PSA), has been shown to be important for synaptic plasticity, as demonstrated by impaired LTP and learning in mice deficient in polysialyltransferase enzymes necessary for adding PSA to the NCAM protein as well as in wildtype mice after enzymatic removal of PSA. It is suggested that NCAM and its PSA moiety are involved in synaptic remodeling in LTP and learning, possibly by modulating signal transduction pathways as well as by mediating and permitting adhesive changes in an activity-dependent manner.

Extracellular Protein Interactions Mediated by the Neural Cell Adhesion Molecule, NCAM: Heterophilic Interactions Between NCAM and Cell Adhesion Molecules, Extracellular Matrix Proteins, and Viruses

Cell adhesion molecules (CAMs) mediate cell-to-cell interactions and interactions between cells and the extracellular matrix (ECM). The neural cell adhesion molecule (NCAM), a prototypic member of the immunoglobulin (Ig) superfamily of CAMs, mediates adhesion through homophilic and heterophilic interactions, thereby modulating a range of biological processes. This review summarizes interactions between NCAM and other CAMs and ECM proteins. Additionally, the role of NCAM as a receptor for rabies virus, and its implications in rabies infections is briefly described. Interactions between NCAM and its heterophilic partners involve most of the NCAM extracellular modules and are mediated via amino acids and carbohydrates. The interactions promote cell adhesion and trigger signal transduction and alterations in cytoskeletal dynamics and organization. Heterophilic NCAM interactions may modulate, or be modulated by, homophilic NCAM interactions. Furthermore, some of the interactions are mutually exclusive, whereas others might lead to the formation of multimeric protein complexes. Consequently, biological processes affected by NCAM interactions are regulated in a complex manner involving many extracellular protein interactions.

WITHDRAWN: Role of NCAM in Spine Dynamics and Synaptogenesis.

Increasing evidence indicates that adhesion molecules are critically involved in the regulation of mechanisms of synaptic plasticity including synapse formation, but also synaptic remodeling associated to changes in synaptic strength. Among these, the Neural Cell Adhesion Molecule (NCAM) and its polysialylated form PSA-NCAM are important candidates. Here we review recent results that point to a possible role of these two molecules in regulating the structural properties of excitatory synapses and namely the composition and stability of the postsynaptic density, thereby accounting for their contribution to mechanisms of synaptogenesis and activity-dependent synaptic plasticity.

Neural-cell adhesion molecule (NCAM) expression by immature and tumor-derived endothelial cells favors cell organization into capillary-like structures

The neural cell adhesion molecule (NCAM) is widely expressed during embryogenesis, down-regulated in the course of differentiation to be re-expressed during progression of some tumors. We here found that renal tumor-derived endothelial cells (TEC) but not normal endothelial cells (HMEC) expressed NCAM. In TEC, NCAM expression was regulated by the renal embryonic transcription factor PAX2, as transfection with PAX2 antisense abrogated NCAM expression. NCAM stimulation with an agonistic synthetic NCAM peptide enhanced apoptosis resistance and increased ability of TEC to organize in vessel-like structures. The angiogenic effect of NCAM peptide was, at least in part, mediated by the association of NCAM and FGFR1. HMEC transiently acquired NCAM when organized in vessel-like structures after VEGF stimulation or when transfected with PAX2 gene. During the process of VEGF-induced endothelial differentiation of renal stem cells and of circulating endothelial progenitors, NCAM was transiently expressed to disappear at complete endothelial maturation. Targeting NCAM with a saporin-conjugated peptide induced a cytotoxic effect on TEC but not on HMEC. In conclusion, we identified a new role of NCAM in tumor neo-angiogenesis relevant for endothelial cell organization into capillary-like structures. In addition, we found that NCAM expression was associated with an immature phenotype of endothelial cells.

The role of NCAM in remyelination.

The neural cell adhesion molecule (NCAM) is expressed by myelinating precursor cells in neonatal mouse spinal cord and by remyelinating cells after chemically induced demyelination in adult mouse. It shows tempting suggestions about its possible involvement in the reparative mechanisms and the remyelination processes that take place in multiple sclerosis (MS). In fact, its levels progressively increase in the cerebrospinal fluid (CSF) of acute MS patients subjected to steroid treatment, paralleling the progressive clinical improvement after the attack. Such an increase is not found in acute MS patients not treated with steroids nor in non-acute patients subjected to the same steroid treatment.

μ-Opioid receptor gene expression: the role of NCAM

We have investigated the mechanisms regulating the expression of the μ-opioid receptor, using P19 mouse embryonal carcinoma cells, which normally lack this receptor, but which can be induced to express it in aggregated cells by retinoic acid treatment. The expression level of μ-opioid receptor mRNA was found to be closely correlated with aggregation status, and more specifically by cell to cell interaction requiring neural cell adhesion molecules (NCAM). We showed that NCAM activates the μ-opioid receptor gene through a pathway involving phospholipase C–arachidonic acid–calcium channel–calcium/calmodulin kinase II. A similar pathway was previously shown to promote neurite outgrowth, however, with distinct specificity, including the role of calcium channels. Activation of L-type calcium channels elevated μ-opioid receptor expression, while N-type-channel activity had the opposite effect. The effect of anti-NCAM-antibody treatment was not due to retardation of general neural development and was specific to the μ-opioid receptor gene. Our results indicate that the P19 system is an useful model to study the expression of the μ-opioid receptor gene.

Expression of neural cell adhesion molecule in human liver development and in congenital and acquired liver diseases.

In the liver, neural cell adhesion molecule (NCAM) is a marker of immature cells committed to the biliary lineage and is expressed by reactive bile ductules in human liver diseases. We investigated the possible role of NCAM in the development of intrahepatic bile ducts and aimed at determining whether immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases. Therefore, we performed immunohistochemistry for NCAM and bile duct cell markers cytokeratin 7 and cytokeratin 19 on frozen sections of 85 liver specimens taken from 14 fetuses, 10 donor livers, 18 patients with congenital liver diseases characterized by ductal plate malformations (DPMs), and 43 cirrhotic explant livers. Duplicated ductal plates and incorporating bile ducts during development showed a patchy immunoreactivity for NCAM, while DPMs were continuously positive for NCAM. Bile ducts showing complete or patchy immunoreactivity for NCAM were found in cirrhotic livers, with higher frequency in biliary than in posthepatitic cirrhosis. Our results suggest that NCAM may have a function in the development of the intrahepatic bile ducts and that NCAM-positive immature biliary cells can contribute to the repair of damaged bile ducts in chronic liver diseases.

N-CAM is not required for initiation of secondary chondrogenesis: the role of N-CAM in skeletal condensation and differentiation.

Condensation precedes chondrogenic differentiation during development of primary cartilage. While neural cell adhesion molecule (N-CAM) enhances condensation, it is unclear whether N-CAM is also required for initiation of chondrogenic differentiation. In this study, the role of N-CAM in secondary chondrogenesis from periosteal cells of the quadratojugal (QJ) from embryonic chicks was studied using several in vitro approaches. The QJ is a membrane bone and so is not preceded by cartilage formation during development. However, QJ periosteal cells can differentiate into chondrocytes to form secondary cartilage in vivo. When QJ periosteal cells were enzymatically released and plated in low density monolayer, clonal or agarose cultures, chondrogenesis was initiated in the absence of N-CAM expression. Furthermore, overexpression of the N-CAM gene in periosteal cells in monolayer culture significantly reduced the number of chondrocyte colonies, suggesting that N-CAM inhibits secondary chondrogenesis. In contrast, and consistent with expression in vivo, N-CAM is expressed during osteogenesis from QJ periosteal cells and mandibular mesenchyme in vitro. These results are discussed in relation to the role of N-CAM in osteogenesis and in primary and secondary condensation.

Neural Cell Adhesion Molecule in Adenoid Cystic Carcinoma Invading the Skull Base

Neural cell adhesion molecules (N‐CAMs) are expressed in neuromuscular tissues, neuroblastoma, and small cell lung carcinoma. Adenoid cystic carcinoma may invade the skull by either direct extension or neural involvement, particularly along the second and third divisions of the trigeminal nerve (V2 and V3). Eighteen patients with adenoid cystic carcinoma that invaded the skull base were studied. The tumors were graded into predominantly solid (3), cribriform (11), or tubular‐trabecular (4) patterns, and neural involvement was evaluated histologically. Paraffin sections were examined by use of monoclonal antibodies for N‐CAM and Ki‐67, a proliferation marker, with the avidin‐biotin‐peroxidase method. Fifteen (83%) tumors showed perineural involvement; in the remaining three cases no nerves were present for histologic examination. Fourteen (93%) of 15 tumors with perineural involvement were reactive with N‐CAM. Proliferation, measured by the presence of nuclear Ki‐67, was markedly increased in tumors with predominantly solid patterns. We demonstrated that N‐CAM is expressed in adenoid cystic carcinoma. The role of N‐CAM as a neurodeterminant that facilitates the spread of adenoid cystic carcinoma along nerves, however, remains unanswered and warrants further study.

Neural cell adhesion molecule in adenoid cystic carcinoma invading the skull base

Neural cell adhesion molecules (N-CAMs) are expressed in neuromuscular tissues, neuroblastoma, and small cell lung carcinoma. Adenoid cystic carcinoma may invade the skull by either direct extension or neural involvement, particularly along the second and third divisions of the trigeminal nerve (V2 and V3). Eighteen patients with adenoid cystic carcinoma that invaded the skull base were studied. The tumors were graded into predominantly solid (3), cribriform (11), or tubular-trabecular (4) patterns, and neural involvement was evaluated histologically. Paraffin sections were examined by use of monoclonal antibodies for N-CAM and Ki-67, a proliferation marker, with the avidin-biotin-peroxidase method. Fifteen (83%) tumors showed perineural involvement; in the remaining three cases no nerves were present for histologic examination. Fourteen (93%) of 15 tumors with perineural involvement were reactive with N-CAM. Proliferation, measured by the presence of nuclear Ki-67, was markedly increased in tumors with predominantly solid patterns. We demonstrated that N-CAM is expressed in adenoid cystic carcinoma. The role of N-CAM as a neurodeterminant that facilitates the spread of adenoid cystic carcinoma along nerves, however, remains unanswered and warrants further study. (Otolaryngol Head Neck Surg 1997;117:453-8.)