Expression of integrins and CD44 isoforms in non-Hodgkin's lymphomas: CD44 variant isoforms are preferentially expressed in high-grade malignant lymphomas

1994 ◽  
Vol 174 (2) ◽  
pp. 89-100 ◽  
Author(s):  
Hans-Joachim Terpe ◽  
Rita Koopmann ◽  
Beat A. Imhof ◽  
Ursula Günthert
Keyword(s):  
High Grade ◽  
Malignant Lymphomas ◽  
Cd44 Isoforms ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
Hodgkin's Lymphomas ◽  
Cd44 Variant Isoforms

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 Expression and modulation of CD44 variant isoforms in humans

1994 ◽  
Vol 124 (1) ◽  
pp. 71-82 ◽  
Author(s):  
CR Mackay ◽  
HJ Terpe ◽  
R Stauder ◽  
WL Marston ◽  
H Stark ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Metastasis ◽  
Cell Types ◽  
The Body ◽  
Basal Cells ◽  
Ifn Gamma ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
And Function ◽  
Cd44 Variant Isoforms

CD44 is a ubiquitous surface molecule that exists as a number of isoforms, generated by alternative splicing of 10 "variant" exons. Little is known about the expression and function of the variant isoforms, except that certain isoforms may play a role in cancer metastasis. We produced mAbs against CD44 variant regions encoded by exons 4v, 6v, and 9v, by immunizing mice with a fusion protein spanning variant exons 3v to 10v. A comprehensive analysis of human tissues revealed that CD44 variant isoforms were expressed widely throughout the body, principally by epithelial cells. However there was differential expression of CD44 variant exons by different epithelia. Most epithelia expressed exon 9v, but much fewer expressed 6v or 4v. The regions of epithelia that expressed the highest levels of the variant isoforms were the generative cells, particularly the basal cells of stratified squamous epithelium, and of glandular epithelium. CD44 variant isoforms were also expressed differentially by leukocytes, with CD44-9v expressed at very low levels and CD44-6v and 4v virtually absent. However, CD44-9v and CD44-6v were the main variants that were transiently upregulated on T cells after mitogenic stimulation and on myelomonocytic cell lines by TNF alpha and IFN gamma treatment. Some epithelial cell lines could preferentially upregulate CD44-6v upon IFN gamma incubation. These results show that CD44 variant isoforms are expressed much more widely than first appreciated, and that expression of the variant isoforms on some cell types can be modulated by particular cytokines.

CD44 variant isoforms control experimental autoimmune encephalomyelitis by affecting the lifespan of the pathogenic T cells

2013 ◽  
Vol 27 (9) ◽  
pp. 3683-3701 ◽  
Author(s):  
Lizette Ghazi‐Visser ◽  
Jon D. Laman ◽  
Sabine Nagel ◽  
Marjan Meurs ◽  
Debby Riel ◽  
...  
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
Cd44 Variant Isoforms ◽  
Experimental Autoimmune

Functional activity of murine CD44 variant isoforms in allergic and delayed type hypersensitivity

1997 ◽  
Vol 57 (1-3) ◽  
pp. 217-223 ◽  
Author(s):  
B Wittig ◽  
S Seiter ◽  
N Föger ◽  
C Schwärzler ◽  
U Günthert ◽  
...  
Keyword(s):  
Functional Activity ◽  
Delayed Type Hypersensitivity ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
Cd44 Variant Isoforms

CD44 variant isoforms are involved in TH1 and TH2 delayed type hypersensitivity

1998 ◽  
Vol 16 ◽  
pp. S4
Author(s):  
Simone Seiter ◽  
Marc Rösel ◽  
Uulla Günthert ◽  
Wolfgang Tilgen ◽  
Margot Zöller
Keyword(s):  
Delayed Type Hypersensitivity ◽  
Cd44 Variant ◽  
Variant Isoforms ◽  
Cd44 Variant Isoforms ◽  
Th1 And Th2
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