scholarly journals Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 264 ◽  
Author(s):  
Inês B. Moreira ◽  
Filipe Pinto ◽  
Catarina Gomes ◽  
Diana Campos ◽  
Celso A. Reis
Keyword(s):  
Gastric Cancer ◽  
Monoclonal Antibodies ◽  
Protein Detection ◽  
Protein Glycosylation ◽  
Major Protein ◽  
Cd44 Isoforms ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
Cancer Models ◽  
Protein Splice

CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes. The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells. Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies. However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded. In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies. We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection. These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.

scholarly journals CD44 variant isoforms in non-Hodgkin's lymphoma: a new independent prognostic factor

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2885-2899 ◽  
Author(s):  
R Stauder ◽  
W Eisterer ◽  
J Thaler ◽  
U Gunthert
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Lymphoid Tissues ◽  
Cd44 Isoforms ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
Non Hodgkin’S Lymphoma ◽  
Tumor Dissemination ◽  
Non Hodgkin's Lymphoma ◽  
Cd44 Variant Isoforms

Isoforms of the transmembrane glycoprotein CD44, generated by alternative RNA splicing, have been correlated to tumor dissemination. For evaluation of the potential role of CD44 variant isoforms in non- Hodgkin's lymphoma (NHL), the presence of CD44 isoforms was analyzed in a large panel of reactive and neoplastic lymphoid tissues by immunohistochemical staining, as well as detection of CD44 variant RNAs by the reverse transcriptase-polymerase chain reaction. Whereas the CD44 standard or hematopoietic isoform (CD44s), devoid of the variant regions, was expressed in all leukocyte subpopulations, the variant isoforms (CD44v) showed a highly restricted pattern of expression, mainly observed in epithelial layers of lymphoid tissues and subpopulations of leukocytes after stimulation. In addition to a strong expression of CD44s, variant isoforms containing CD44–6v in combination with other variant exons were observed predominantly in aggressive lymphoma and were associated with a shorter overall survival of patients (n = 138; P < .0001). Moreover, multivariate analysis indicated CD44–6v as a new independent prognostic parameter in high grade NHL in comparison with the risk groups defined by the International NHL Lymphoma Prognostic Factors Project (N Engl J Med 329:987, 1993).

scholarly journals The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Ranjeeta Thapa ◽  
George D. Wilson
Keyword(s):  
Tumor Cell ◽  
Cancer Progression ◽  
Chemotherapy Resistance ◽  
Cd44 Isoforms ◽  
Cd44 Variant ◽  
Tumor Cell Migration ◽  
Variant Isoforms ◽  
Oncogenic Pathways ◽  
Targeted Inhibition ◽  
Cd44 Variant Isoforms

CD44 is a cell surface HA-binding glycoprotein that is overexpressed to some extent by almost all tumors of epithelial origin and plays an important role in tumor initiation and metastasis. CD44 is a compelling marker for cancer stem cells of many solid malignancies. In addition, interaction of HA and CD44 promotes EGFR-mediated pathways, consequently leading to tumor cell growth, tumor cell migration, and chemotherapy resistance in solid cancers. Accumulating evidence indicates that major HA-CD44 signaling pathways involve a specific variant of CD44 isoforms; however, the particular variant almost certainly depends on the type of tumor cell and the stage of the cancer progression. Research to date suggests use of monoclonal antibodies against different CD44 variant isoforms and targeted inhibition of HA/CD44-mediated signaling combined with conventional radio/chemotherapy may be the most favorable therapeutic strategy for future treatments of advanced stage malignancies. Thus, this paper briefly focuses on the association of the major CD44 variant isoforms in cancer progression, the role of HA-CD44 interaction in oncogenic pathways, and strategies to target CD44-overexpressed tumor cells.

scholarly journals Development of a Novel Orthotopic Gastric Cancer Mouse Model

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Wonyoung Kang ◽  
Leigh Maher ◽  
Michael Michaud ◽  
Seong-Woo Bae ◽  
Seongyeong Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mouse Models ◽  
Cancer Metastasis ◽  
Soft Tissues ◽  
Tumor Formation ◽  
Cancer Model ◽  
Orthotopic Model ◽  
Cancer Models ◽  
Organotropic Metastasis ◽  
Nsg Mouse

Abstract Background Gastric cancer metastasis is a highly fatal disease with a five-year survival rate of less than 5%. One major obstacle in studying gastric cancer metastasis is the lack of faithful models available. The cancer xenograft mouse models are widely used to elucidate the mechanisms of cancer development and progression. Current procedures for creating cancer xenografts include both heterotopic (i.e., subcutaneous) and orthotopic transplantation methods. Compared to the heterotopic model, the orthotopic model has been shown to be the more clinically relevant design as it enables the development of cancer metastasis. Although there are several methods in use to develop the orthotopic gastric cancer model, there is not a model which uses various types of tumor materials, such as soft tissues, semi-liquid tissues, or culture derivatives, due to the technical challenges. Thus, developing the applicable orthotopic model which can utilize various tumor materials is essential. Results To overcome the known limitations of the current orthotopic gastric cancer models, such as exposure of tumor fragments to the neighboring organs or only using firm tissues for the orthotopic implantation, we have developed a new method allowing for the complete insertion of soft tissue fragments or homogeneously minced tissues into the stomach submucosa layer of the immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mouse. With this completely-closed transplantation method, tumors with various types of tissue may be used to establish orthotopic gastric cancer models without the risks of exposure to nearby organs or cell leakage. This surgical procedure was highly reproducible in generating forty-eight mouse models with a surgery success rate of 96% and tumor formation of 93%. Among four orthotopic patient-derived xenograft (PDX) models that we generated in this study, we verified that the occurrence of organotropic metastasis in either the liver or peritoneal cavity was the same as that of the donor patients. Conclusion Here we describe a new protocol, step by step, for the establishment of orthotopic xenograft of gastric cancer. This novel technique will be able to increase the use of orthotopic models in broader applications for not only gastric cancer research but also any research related to the stomach microenvironment.

scholarly journals Structural Variability of CD44v Molecules and Reliability of Immunodetection of CD44 Isoforms Using mAbs Specific for CD44 Variant Exon Products

1999 ◽  
Vol 154 (1) ◽  
pp. 291-300 ◽  
Author(s):  
Marco Paolo Martegani ◽  
Fabrizio Del Prete ◽  
Alessandra Gasbarri ◽  
Pier Giorgio Natali ◽  
Armando Bartolazzi
Keyword(s):  
Cd44 Isoforms ◽  
Variant Exon ◽  
Cd44 Variant ◽  
Structural Variability
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