scholarly journals Clinical and Biological Characteristics of Medullary and Extramedullary Plasma Cell Dyscrasias

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 629
Author(s):  
Snjezana Janjetovic ◽  
Philipp Lohneis ◽  
Axel Nogai ◽  
Derya Balci ◽  
Leo Rasche ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Molecular Mechanisms ◽  
Biological Characteristics ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
Similar Frequency ◽  
Cytogenetic Aberrations ◽  
A Cell ◽  
Plasma Cell Dyscrasias ◽  
Extramedullary Plasmocytoma

Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p < 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4;14) and t(14;16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP.

Cloning of the gene encoding TROP-2, a cell-surface glycoprotein expressed by human carcinomas

1995 ◽  
Vol 62 (5) ◽  
pp. 610-618 ◽  
Author(s):  
Mara Fornaro ◽  
Roberta Dell' Arciprete ◽  
Manuela Stella ◽  
Cecilia Bucci ◽  
Michele Nutini ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Glycoprotein ◽  
Gene Encoding ◽  
Cell Surface Glycoprotein ◽  
Human Carcinomas ◽  
A Cell

scholarly journals 2B4, the Natural Killer and T Cell Immunoglobulin Superfamily Surface Protein, Is a Ligand for CD48

1998 ◽  
Vol 188 (11) ◽  
pp. 2083-2090 ◽  
Author(s):  
Marion H. Brown ◽  
Kent Boles ◽  
P. Anton van der Merwe ◽  
Vinay Kumar ◽  
Porunelloor A. Mathew ◽  
...  
Keyword(s):  
Natural Killer ◽  
Genetic Manipulation ◽  
Surface Protein ◽  
Surface Glycoprotein ◽  
Immunoglobulin Superfamily ◽  
Lymphocyte Function ◽  
Cell Surface Glycoprotein ◽  
Extracellular Region ◽  
Additional Ligand ◽  
A Cell

2B4 is a cell surface glycoprotein related to CD2 and implicated in the regulation of natural killer and T lymphocyte function. A recombinant protein containing the extracellular region of mouse (m)2B4 attached to avidin-coated fluorescent beads bound to rodent cells, and binding was completely blocked by CD48 monoclonal antibodies (mAbs). Using surface plasmon resonance, we showed that purified soluble mCD48 bound m2B4 with a six- to ninefold higher affinity (Kd ≈ 16 μM at 37°C) than its other ligand, CD2. Human CD48 bound human 2B4 with a similar affinity (Kd ≈ 8 μM). The finding of an additional ligand for CD48 provides an explanation for distinct functional effects observed on perturbing CD2 and CD48 with mAbs or by genetic manipulation.

scholarly journals Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 973
Author(s):  
Brendan L. Hagerty ◽  
Guillaume J. Pegna ◽  
Jian Xu ◽  
Chin-Hsien Tai ◽  
Christine Alewine
Keyword(s):  
Solid Tumors ◽  
Clinical Results ◽  
Surface Glycoprotein ◽  
Future Directions ◽  
Cell Surface Glycoprotein ◽  
Therapeutic Development ◽  
A Cell ◽  
Recombinant Immunotoxins ◽  
Strong Body ◽  
Anti Tumor Activity

Mesothelin (MSLN) is a cell surface glycoprotein normally expressed only on serosal surfaces, and not found in the parenchyma of vital organs. Many solid tumors also express MSLN, including mesothelioma and pancreatic adenocarcinoma. Due to this favorable expression profile, MSLN represents a viable target for directed anti-neoplastic therapies, such as recombinant immunotoxins (iToxs). Pre-clinical testing of MSLN-targeted iTox’s has yielded a strong body of evidence for activity against a number of solid tumors. This has led to multiple clinical trials, testing the safety and efficacy of the clinical leads SS1P and LMB-100. While promising clinical results have been observed, neutralizing anti-drug antibody (ADA) formation presents a major challenge to overcome in the therapeutic development process. Additionally, on-target, off-tumor toxicity from serositis and non-specific capillary leak syndrome (CLS) also limits the dose, and therefore, impact anti-tumor activity. This review summarizes existing pre-clinical and clinical data on MSLN-targeted iTox’s. In addition, we address the potential future directions of research to enhance the activity of these anti-tumor agents.

ADAM23 is a cell-surface glycoprotein expressed by central nervous system neurons

2004 ◽  
Vol 78 (5) ◽  
pp. 647-658 ◽  
Author(s):  
Alexander P. Goldsmith ◽  
Samuel J. Gossage ◽  
Charles ffrench-Constant
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Surface ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
A Cell

scholarly journals AG alpha 1 is the structural gene for the Saccharomyces cerevisiae alpha-agglutinin, a cell surface glycoprotein involved in cell-cell interactions during mating.

1989 ◽  
Vol 9 (8) ◽  
pp. 3155-3165 ◽  
Author(s):  
P N Lipke ◽  
D Wojciechowicz ◽  
J Kurjan
Keyword(s):  
Cell Surface ◽  
Fusion Protein ◽  
Structural Gene ◽  
Signal Sequence ◽  
Positive Control ◽  
Complementation Group ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
Amino Terminal ◽  
A Cell

We have cloned the alpha-agglutinin structural gene, AG alpha 1, by the isolation of alpha-specific agglutination-defective mutants, followed by isolation of a complementing plasmid. Independently isolated alpha-specific agglutination-defective mutations were in a single complementation group, consistent with biochemical results indicating that the alpha-agglutinin is composed of a single polypeptide. Mapping results suggested that the complementation group identified by these mutants is allelic to the ag alpha 1 mutation identified previously. Expression of AG alpha 1 RNA was alpha specific and inducible by a-factor. Sequences similar to the consensus sequences for positive control by MAT alpha 1 and pheromone induction were found upstream of the AG alpha 1 initiation codon. The AG alpha 1 gene could encode a 650-amino-acid protein with a putative signal sequence, 12 possible N-glycosylation sites, and a high proportion of serine and threonine residues, all of which are features expected for the alpha-agglutinin sequence. Disruption of the AG alpha 1 gene resulted in failure to express alpha-agglutinin and loss of cellular agglutinability in alpha cells. An Escherichia coli fusion protein containing 229 amino acids of the AG alpha 1 sequence was recognized by an anti-alpha-agglutinin antibody. In addition, the ability of this antibody to inhibit agglutination was prevented by this fusion protein. These results indicate that AG alpha 1 encodes alpha-agglutinin. Features of the AG alpha 1 gene product suggest that the amino-terminal half of the protein contains the a-agglutinin binding domain and that the carboxy-terminal half contains a cell surface localization domain, possibly including a glycosyl phosphatidylinositol anchor.

Differentiation defective mutants of skeletal myoblasts altered in a gelatin-binding glycoprotein

1987 ◽  
Vol 65 (9) ◽  
pp. 767-775 ◽  
Author(s):  
George A. Cates ◽  
Devki Nandan ◽  
Anne M. Brickenden ◽  
Bishnu D. Sanwal
Keyword(s):  
Cell Surface ◽  
Molecular Mass ◽  
Surface Glycoprotein ◽  
Myoblast Differentiation ◽  
Wild Type ◽  
Cell Surface Glycoprotein ◽  
Adhesion Properties ◽  
Normal Rat ◽  
A Cell ◽  
Myoblast Cell

We have previously described a myoblast cell surface glycoprotein of the molecular mass 46 000 (gp46), which is associated with myoblast differentiation. In this report we demonstrate that gp46 binds specifically to gelatin-Sepharose and in this respect is similar to a glycoprotein of the molecular mass 47 000, which has earlier been described as a cell surface localized protein in mouse parietal endoderm cells and in chick embryo fibroblasts. To ascertain the relationship of gp46 to myoblast differentiation, wild-type L6 myoblasts, as well as two concanavalin A (ConA) resistant, differentiation-negative, myoblast mutants (D-1 and C-8), were examined for gp46 expression. In the mutant designated D-1, which has a defect in dolichol mannosyl transferase, both mannose incorporation into gp46 and ConA binding to gp46 was reduced compared with L6, without markedly affecting the gelatin adhesion properties of gp46. Western blotting with a monoclonal antibody against gp46 was used to show that the expression of gp46 was normal in D-1 but was reduced in mutant C-8 compared with L6. Reduction occurred both in the plasma membrane and endoplasmic reticulum fractions of C-8 compared with wild-type L6. In L6 myoblasts, the expression of gp46 remained constant during myoblast replication and fusion but decreased markedly postfusion. In the nonfusing myoblast mutants D-1 and C-8 and in wild-type L6 cells that were prevented from fusing by treatment with 5-bromo-2′-deoxyuridine, the expression of gp46 remained invariant. We suggest that collagen interactions, mediated by gp46, are important for normal rat skeletal muscle differentiation.

scholarly journals Variations in the cytoskeletal interaction and posttranslational modification of the CD44 homing receptor in macrophages.

1991 ◽  
Vol 115 (5) ◽  
pp. 1283-1292 ◽  
Author(s):  
R L Camp ◽  
T A Kraus ◽  
E Puré
Keyword(s):  
Structural Changes ◽  
Inflammatory Responses ◽  
Surface Glycoprotein ◽  
Structural Variations ◽  
Cell Surface Glycoprotein ◽  
A Cell ◽  
Indirect Association ◽  
Macrophage Populations ◽  
Intracellular Domains ◽  
Two Populations

Murine CD44 is a cell surface glycoprotein that is thought to play a role in leukocyte migration. We studied the structure and expression of CD44 on two populations of macrophages: those that reside in the peritoneum of unprimed mice, and those that have been elicited to migrate into the peritoneum by the intraperitoneal injection of agents that cause localized inflammatory responses. Our studies reveal structural variations in both the extracellular and intracellular domains of CD44 expressed by these two macrophage populations. The form of CD44 in elicited macrophages has an apparent molecular mass that is approximately 5 kD greater and more heterogenous than that in resident macrophages. This structural changes is posttranslational, extracellular, and apparently reflects increases in N-linked glycosylation. It is also specific for CD44 and does not occur with several other glycoproteins examined. This novel regulation of glycosylation may play an important role in the ability of CD44 to bind to different substrates, particularly lectin-like ligands. In addition, we demonstrate that CD44 in resident macrophages is divided into two pools, one containing nonphosphorylated, cytoskeletally associated CD44, and one containing phosphorylated, unassociated CD44. In contrast, CD44 on the surface of elicited macrophages does not associate with the cytoskeleton. The attachment of CD44 to the cytoskeleton involves either direct or indirect association with actin. The regulated association of CD44 with the cytoskeleton suggests that it may influence or be influenced by macrophage mobility.

scholarly journals Kidney disease associated with plasma cell dyscrasias

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1397-1404 ◽  
Author(s):  
Eliot C. Heher ◽  
Nelson B. Goes ◽  
Thomas R. Spitzer ◽  
Noopur S. Raje ◽  
Benjamin D. Humphreys ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Cell ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Light Chains ◽  
Free Light Chains ◽  
Monoclonal Immunoglobulin ◽  
Plasma Cell Dyscrasias ◽  
Made In

Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve.

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