Detection of Metastatic Tumor Cells in Bone Marrow
Adrian P. Gee in BONE MARROW PROCESSING and PURGING, 2020
Neuroblastoma is a tumor with stable antigen expression; consequently, immunologic methods have been relatively easy to develop for the detection of marrow metastases. One of the most important of these antigens is GD2, which is a tumor-specific ganglioside found on the surface of greater than 90% of neuroblastoma cell populations.14,17 Antibodies to this antigen have been useful for identification of marrow metastases, marrow purging, and in vivo therapy.14,17,43–46 Another predominant antigen is the neural cell adhesion molecule (NCAM), which is expressed by most neuroblasts, and binds to antibodies that are also used for detection and purging.46,47 Other important antigens include those expressed by fetal brain (459, HSAN, UJ13A, and UJ167.11).14,16,21 Antibodies that bind to cytoplasmic antigens have not played an extensive role in tumor detection for neuroblastoma. The only one is an antibody that binds to neuron-specific enolase. This enzyme is found in many neuronal cells and is expressed by greater than 90% of neuroblastoma cells.25 The disadvantages of using this antibody are cross-reactivity with megakaryocytes and the inability to distinguish single tumor cells on immunoperoxidase staining.
Retinal stem cell research
A Peyman MD Gholam, A Meffert MD Stephen, D Conway MD FACS Mandi, Chiasson Trisha in Vitreoretinal Surgical Techniques, 2019
CNS stem or progenitor cells also express many less specific markers. These include the intermediate filament protein vimentin, the proliferation marker Ki-67, the cell cycle protein cyclin D1, and various forms of the surface adhesion molecule NCAM (neural cell adhesion molecule, CD56), as well as the surface markers CD9 and CD81, both of which are members of the tetraspanin family of transmembrane proteins.5 While it seems increasingly likely that no single unique marker for NSCs will be identified, the use of multiple positive and negative markers in combination may provide a way around this problem. Undoubtedly, a more comprehensive understanding of cellular transcriptional activity will allow investigators to better resolve the ontogenetic status of cells of interest.
Transformation of Colon Epithelial Cells
George E. Milo, Bruce C. Casto, Charles F. Shuler in Transformation of Human Epithelial Cells: Molecular and Oncogenetic Mechanisms, 2017
Another allelic loss in colorectal tumors occurs in chromosome 18q. Such deletions have been detected in approximately 70% of the carcinomas and 50% of late adenomas.24,29 As noted above, chromosome deletions frequently indicate the presence of tumor suppressor genes. Recently, a candidate gene, termed DCC, has been identified as a possible tumor suppressor gene in chromosome 18q.29 This gene apparently encodes a protein with amino acid sequences similar to neural cell adhesion molecules and is related to plasma membrane glycoproteins. The identification of the gene was based on several parameters:29 (1) one allele of the DCC gene was found deleted in 71% of the colorectal neoplasms, (2) the DCC gene was expressed in all normal mucosal tissues, but its expression was greatly reduced or absent in 88% of colon tumor cell lines, and (3) somatic mutations of the DCC gene occurred in almost 13% of the carcinomas. The mechanisms by which the DCC gene is involved in colorectal neoplasms is not understood; reduction in its expression could reduce the growth-inhibiting properties and other cell surface properties. Much evidence exists to suggest that neoplastic transformation involves cell surface alterations. For instance, loss of contact inhibition of growth in vitro is considered an important phenotype of preneoplastic and/or neoplastic transformation; malignant transformation is believed to involve cell-cell and cell-basement membrane interactions. Further studies, however, are necessary to define the role of the DCC gene in colorectal carcinoma.
Preparation and anti-cancer evaluation of promiximab-MMAE, an anti-CD56 antibody drug conjugate, in small cell lung cancer cell line xenograft models
Published in Journal of Drug Targeting, 2018
Lin Yu, Yuqin Yao, Yuxi Wang, Shijie Zhou, Qinhuai Lai, Ying Lu, Yu Liu, Ruirui Zhang, Ruixue Wang, Chuang Liu, Lantu Gou, Xiaoxin Chen, Yamei Yu, Qiang Chen, Jinliang Yang
Neural cell adhesion molecule (NCAM), also called CD56is a kind of membrane glycoprotein that belongs to immunoglobulin (Ig) superfamily [11–14]. It is highly expressed and is involved in cell migration, invasion and metastasis of SCLC cells [15]. CD56 is considered as a potential target of ADCs because of its function in mediating endocytosis of cancer cells [16,17]. Currently, there are two ADCs under clinical trials for the treatment SCLC. SC16LD6.5 (known as Rova-T), is produced by conjugating a humanised anti-DLL3 monoclonal antibody to a DNA-damaging pyrrolobenzodiazepine (PBD) dimer toxin has entered clinical Phase I/II trials for SCLC (NCT01901653, 16) [18]. The other one is Lorvotuzumab Mertansine (IMGN901), an anti-CD56 DM1 conjugate, comprised of a humanised CD56 antibody conjugated to microtubule inhibitor DM1 [19].
Common markers of testicular Sertoli cells
Published in Expert Review of Molecular Diagnostics, 2021
Xu You, Qian Chen, Ding Yuan, Changcheng Zhang, Haixia Zhao
NCAM is a type of cell surface membrane glycoprotein that mediates cell-to-cell communication and cell-to-extracellular matrix adhesion. It is widely expressed in the nervous system, blood, kidney, muscle, and reproductive system [2,33], and in several tumor tissues such as neuroblastoma and primary brain tumors [34]. NCAM is ubiquitously observed at the boundaries between adjacent Sertoli cells, and between Sertoli cells and gonocytes within the seminiferous tubules of Sprague-Dawley (SD) rats from birth to day 10, and then NCAM expression is gradually downregulated and eventually disappears during the maturation of Sertoli cells in vivo [35]. Other studies showed that NCAM is indeed expressed in the fetus or in immature Sertoli cells, and is involved in the regulation of the adhesion and migration of gonocytes from the lumen to the basement membrane [36,37], the interaction of Sertoli cell-gonocyte during testicular development, germ cell-Sertoli cell adhesion, and the promotion of immature Sertoli cell proliferation [38]. Therefore, NCAM can be considered an immature Sertoli cell marker, which is also downregulated by treatment with thyroid hormone (T3) [36].
Delivery of neurotrophic factors in the treatment of age-related chronic neurodegenerative diseases
Published in Expert Opinion on Drug Delivery, 2020
Smrithi Padmakumar, Maie S. Taha, Ekta Kadakia, Benjamin S. Bleier, Mansoor M. Amiji
This family consists of homodimeric polypeptides: GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN), which also belong to the transforming growth factor β superfamily. GDNF is the first identified member in this family with an important role in survival of midbrain dopaminergic neurons in a specific manner [25]. Other GFLs have shown similar potent protective effects for dopaminergic neurons [26]. GDNF is also considered as one of the most protective factors for motor neurons and has showed a significantly higher benefit than neurotrophins in regenerating sensory axons in a spinal cord injury rat model [27]. GFLs exert their neuroprotective functions both centrally and peripherally, except for PSPN which functions only centrally. GFLs also have roles in synaptic transmission and activity-dependent neuroplasticity. They function by activating RET tyrosine kinase via binding to the GDNF family receptor-α (GFRα) that is anchored to the plasma membrane by glycosyl phosphatidylinositol, which eventually leads to activation of PLCγ, PI3K, and mitogen-activated protein kinase (MAPK) pathways [23]. GDNF binding to neural cell adhesion molecule was also shown to induce signaling for mediating neurite outgrowth [28].