CD44 splice variants: metastases meet lymphocytes
Immunology TodayPublished 1 August 1993
Peter Herrlich, Margot Zöller, Steven T. Pals, Helmut Ponta
Citations261
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
Abstract
Recent discoveries of surface proteins involved in tumor metastasis formation have revived an old hypothesis that tumor cells may acquire, and use for their metastatic spreading, properties which lymphoid cells had developed to defend the organism against foreign antigens. Splice variants of CD44 and integrins are expressed on metastasizing tumor cells and also on leukocytes at defined stages of their differentiation. Expression and function appear to be essential not only for the generation of an immune response but also for the establishment of metastatic tumor colonies.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
CellCD44 is the principal cell surface receptor for hyaluronate
2,442 Citations1990Alejandro Aruffo, Ivan Stamenkovic +3 more
CellA new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells
1,672 Citations1991Ursula Günthert, Martin Hofmann‐Apitius +8 more
Using a monoclonal antibody raised against a surface glycoprotein of the metastasizing rat pancreatic carcinoma cell line BSp73ASML, cDNA clones have been isolated that encode glycoproteins with partial homology to CD44, a presumed adhesion molecule.
Annual Review of MedicineLEUKOCYTE ADHESION DEFICIENCY: An Inherited Defect in the Mac-1, LFA-1, and p150,95 Glycoproteins
1,143 Citations1987D. C. Anderson, Timothy A. Springer
Recognition of the molecular pathogenesis of this disorder has allowed rich insights into the role of cellular adherence reactions in inflammation and host defense.
Annual Review of ImmunologyThe Lymphocyte Function Associated LFA-1, CD2, and LFA-3 Molecules: Cell Adhesion Receptors of the Immune System
1,103 Citations1987Timothy A. Springer, Michael L. Dustin +2 more
This review focuses on LFAI, CD2, and LFA-3, which appear to enhance antigen-specific functions by acting as cell adhesion molecules and the role of CD4 and CD8 is reviewed by Littman.
Immunology TodayLymphocyte interactions with endothelial cells
686 Citations1992Yoji Shimizu, Walter Newman +2 more
The molecules that mediate lymphocyte-endothelial cell adhesion are identified, the underlying principles of lymphocyte migration are described, and a model of the sequence of events that allow a lymphocyte to successfully attach to endothelium and migrate into the surrounding tissue is discussed.
NatureRegulated expression and binding of three VLA (β1) integrin receptors on T cells
630 Citations1990Yoji Shimizu, Gijs A. van Seventer +2 more
The regulated binding of resting CD4+ human T cells to ECM through three VLA integrins is described, including a novel pathway of VLA-6 binding to laminin (LN).
ScienceA Synthetic Peptide from Fibronectin Inhibits Experimental Metastasis of Murine Melanoma Cells
628 Citations1986Martin J. Humphries, Kenneth Olden +1 more
Inhibition by GRGDS was dose-dependent, noncytotoxic, and did not result from an impairment of cellular tumorigenicity, and may function by inhibiting tumor cell retention in the lung since radiolabeled B16-F10 tumor cells injected with the peptide were lost at a substantially greater rate than control cells.
The Journal of Experimental MedicineHyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition.
623 Citations1990Kensuke Miyake, C B Underhill +2 more
Investigation has revealed that hyaluronate is a potential ligand for CD44 and that hyAluronate recognition accounts for the adhesion between B lineage hybridoma and stromal cells.
The EMBO JournalThe hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate‐bearing cells.
580 Citations1991Ivan Stamenkovic, Alejandro Aruffo +2 more
The isolation of a cDNA encoding a distinct CD44 polypeptide expressed by epithelial cells is described, allowing cells transfected with the hematopoietic but not the epithelial form to bind to viable rat lymph node HEV cells in primary culture.
The Journal of Cell BiologyLymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.
543 Citations1987Sirpa Jalkanen, Robert F. Bargatze +2 more
It is shown that antibodies capable of inhibiting human lymphocyte binding to one or more HEV types recognize a common 85- 95-kD lymphocyte surface glycoprotein antigen, defined by the non- blocking monoclonal antibody, Hermes-1, which implies that related molecular mechanisms are involved in several functionally independent cell-cell recognition events that direct lymphocyte traffic.
European Journal of ImmunologyA lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man
427 Citations1986Sirpa Jalkanen, Robert F. Bargatze +2 more
It is demonstrated that the molecule defined by Hermes‐1 either functions as a specific lymphocyte surface receptor for HEV, or is both precisely coregulated and physically and/or functionally associated with such receptors.
ScienceParticipation in Normal Immune Responses of a Metastasis-Inducing Splice Variant of CD44
416 Citations1992Robert H. Arch, Karin G. Wirth +5 more
The observation that a protein domain that is expressed on CD44 and required for the lymphatic spread of tumor cells can catalyze an essential step in the process of lymphocyte activation supports the idea that metastasizing tumor cells mimic lymphocyte behavior.
The Journal of Cell BiologyThe hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins [published erratum appears in J Cell Biol 1991 Feb;112(3):following 513]
364 Citations1990Martine Culty
CD44 appears to have at least two distinct functional domains, one for binding hyaluronate and another involved in interactions with mucosal high endothelial venules, which is implicated in cell adhesion.
The Journal of Cell BiologyA human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps.
349 Citations1993Karl‐Heinz Heider, Martin Hofmann‐Apitius +5 more
The finding that metastasis-related variants are already expressed at a relatively early stage in colorectal carcinogenesis and tumor progression, i.e., in adenomatous polyps, suggests the existence of a yet unknown selective advantage linked to CD44 variant expression.
The Journal of Experimental MedicinePrevention of tumor metastasis formation by anti-variant CD44.
346 Citations1993Simone Seiter, R. Arch +7 more
It is suggested that the mAbInterference with metastatic spread will greatly facilitate the exploration of the function of CD44v and, in particular, may also open new strategies for the therapy of human metastases.
ScienceIn Vitro and in Vivo Consequences of VLA-2 Expression on Rhabdomyosarcoma Cells
327 Citations1991Bosco M. C. Chan, Nariaki Matsuura∥ +3 more
Results show that a specific adhesion receptor (VLA-2) can markedly enhance both experimental and spontaneous metastasis in rhabdomyosarcoma and nude mice.
ScienceA Distinct Endothelial Cell Recognition System That Controls Lymphocyte Traffic into Inflamed Synovium
312 Citations1986Sirpa Jalkanen, Allen C. Steere +2 more
It is suggested that a lymphocyte-endothelial cell recognition system that is distinct from such systems in organized lymphoid tissues directs the extravasation of normal lymphocytes as well as pathologically important effector cells into inflamed synovium.
The Journal of Experimental MedicineDistinct effects of two CD44 isoforms on tumor growth in vivo.
311 Citations1991Man‐Sun Sy, Yichen Guo +1 more
The results suggest that CD44 polypeptides may play an important role in regulating primary and metastatic tumor development in vivo.
The Journal of Experimental MedicineActivated human lymphocytes and aggressive non-Hodgkin's lymphomas express a homologue of the rat metastasis-associated variant of CD44.
305 Citations1993Gerrit Koopman, Karl‐Heinz Heider +6 more
The reaction pattern of various antibodies indicates that these CD44 variants contain the domain encoded by exon v6, which is part of the variant that in the rat confers metastatic capability and it is interesting that overexpression of v6 was also found in several aggressive, but not low-grade, non- Hodgkin's lymphomas.
The Journal of Cell BiologyInhibition of in vitro tumor cell invasion by Arg-Gly-Asp-containing synthetic peptides [published erratum appears in J Cell Biol 1989 Jun;108(6):following 2546]
304 Citations1988Kurt R. Gehlsen
Interactions between RGD-containing extracellular matrix adhesion proteins and cells are necessary for cell invasion through tissues and that fibronectin and type I collagen are important for this process.
Nucleic Acids ResearchSplicing choice from ten variant exons establishes CD44 variability
285 Citations1993Cornelia Tölg, Martin Hofmann‐Apitius +2 more
Comparison of various cDNA clones with different 'inserts' in this variable region with sequences of genomic clones from the mouse has revealed the existence of at least ten exons from which sequences are chosen by alternative splicing.
Journal of Biological ChemistryMultiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain.
236 Citations1992David G. Jackson, J. Thomas Buckley +1 more
It is suggested that a mechanism of alternative exon splicing generates much of the observed structural heterogeneity of CD44 and that the particular set ofCD44 variants expressed in a single cell may represent a precise postal code directing the final destination of migrating cells and metastatic tumors.
PubMedThe two major CD44 proteins expressed on a metastatic rat tumor cell line are derived from different splice variants: each one individually suffices to confer metastatic behavior.
220 Citations1993W. Rudy, Martin Hofmann‐Apitius +5 more
The metastatic pancreas carcinoma cell line BSp73ASML produces a variety of different splice variants of the transmembrane glycoprotein CD44, which suffice to establish metastatic properties in the nonmetastatic tumor cell line, as assayed by the spontaneous metastasis protocol.
The Journal of Cell BiologyAlterations in integrin receptor expression on chemically transformed human cells: specific enhancement of laminin and collagen receptor complexes.
216 Citations1990Shoukat Dedhar, Ronald B. Saulnier
A critical role is indicated for the alpha 6/beta 1 laminin receptor in the invasion of HOS cells through basement membranes and chemical transformation of nontumorigenic human cells to highly tumorigenic cells is associated with an altered pattern of integrin expression which may play a direct role in the increased capacity of these cells to bind and invade through basement membrane.
The Journal of ImmunologyTriggering of the CD44 antigen on T lymphocytes promotes T cell adhesion through the LFA-1 pathway.
183 Citations1990Gerrit Koopman, Yvette van Kooyk +4 more
It is demonstrated that triggering of CD44 on T lymphocytes by anti-CD44 mAb promotes cell adhesion, suggesting that the activation of the LFA-1 pathway via CD44 involves protein kinase C activation and requires an intact cytoskeleton.
The Journal of Experimental MedicineMolecular cloning of CD44R1 and CD44R2, two novel isoforms of the human CD44 lymphocyte "homing" receptor expressed by hemopoietic cells.
180 Citations1991G J Dougherty, P M Landorp +2 more
PCR analysis using primers that flank the inserted region present within CD44R1 identified an additional CD44 isoform, designatedCD44R2, that contains only the last 69 amino acids present within the unique region of CD44C1, and appears to be differentially expressed in various CD44-positive cell lines.
European Journal of ImmunologyMonoclonal antibody to a human brain‐granulocyte‐T lymphocyte antigen probably homologous to the W 3/13 antigen of the rat
180 Citations1980Rosemarie Dalchau, Jean Kirkley +1 more
The monoclonal antibody (F10–44–2) described in this report recognizes an antigen which by quantitative absorption analysis is found predominantly on spleen, lymph node, bone marrow, thymus, granulocytes and brain, the amount of antigen on these tissues being approximately the same within a factor of 2 or 3.
PubMedMonoclonal antibody and synthetic peptide inhibitors of human tumor cell migration.
178 Citations1990Kenneth M. Yamada, Dorothy W. Kennedy +4 more
The results indicate the central importance of several specific beta 1 integrins in human tumor cell migration and show the effectiveness of monoclonal antibody treatment in blocking this process in vitro.
PubMedA link between ras and metastatic behavior of tumor cells : ras induces CD44 promoter activity and leads to low-level expression of metastasis-specific variants of CD44 in CREF cells
148 Citations1993Martin Hofmann‐Apitius, W. Rudy +7 more
A transient increase of CD44v/total CD44 ratio of 3-4 has been determined suggesting that a burst of ras expression, in the genetic background of CREF cells, influences both promoter activity and splice control or accuracy.
Molecular and Cellular BiologySpontaneous fusion in vivo between normal host and tumor cells: possible contribution to tumor progression and metastasis studied with a lectin-resistant mutant tumor.
147 Citations1983Robert S. Kerbel, A. Lagarde +2 more
Cancer and Metastasis ReviewsCell adhesion receptor expression during melanoma progression and metastasis
124 Citations1991Ian R. Hart, Mary L. Birch +1 more
It is illustrated that an understanding of the regulation of melanoma adhesion receptors could provide insights into the process of tumor spread.
The Journal of Cell BiologyMolecular isoforms of murine CD44 and evidence that the membrane proximal domain is not critical for hyaluronate recognition.
124 Citations1992Qi He, Jayne Lesley +3 more
Findings indicate that the NH2-terminal portion of CD44 is sufficient for HA recognition and that this function is not necessarily abrogated by variations which occur in the membrane proximal domain.
The Journal of Experimental MedicineInhibition of tumor growth in vivo with a soluble CD44-immunoglobulin fusion protein.
123 Citations1992M S Sy, Yichen Guo +1 more
It is shown that in vivo tumor formation by human lymphoma Namalwa cells, stably transfected with CD44H, can be suppressed by a soluble humanCD44H-immunoglobulin fusion protein.
Immunology TodayRoll, roll, roll your leucocyte gently down the vein.
115 Citations1992Nancy Hogg
The rapid advances being made in unravelling the biochemistry and function of the three categories of adhesion molecule involved in leucocyte-endothelial-cell interactions, namely selectins, integrins and the Ig super-family molecules, are described.
The Journal of Cell BiologyInvolvement of LFA-1 in lymphoma invasion and metastasis demonstrated with LFA-1-deficient mutants.
110 Citations1989F. F. Roossien, D de Rijk +2 more
It is reported that LFA-1 is also involved in invasion of lymphoma cells into fibroblast monolayers and the invasive potential of the mutant cells in vitro, in both hepatocyte and fibro Blast cultures, was considerably lower than that of parental cells.
The Journal of ImmunologyIdentification of a widely distributed 90-kDa glycoprotein that is homologous to the Hermes-1 human lymphocyte homing receptor.
94 Citations1989Steven T. Pals, Frans B.L. Hogervorst +4 more
Results indicate that the 90-kDa glycoprotein homologues of the Hermes-1 human lymphocyte homing receptor are expressed on hemopoietic tissues as well as on a number of nonhemopoetic tissues and tumor cell lines.
Immunological ReviewsMechanisms of Human Lymphocyte Migration and their Role in the Pathogenesis of Disease
93 Citations1989Steven T. Pals, E. van der Horst +2 more
Evidence indicating that adhesive interactions between recirculating lymphocytes and the wall of high endothelial venules (HEV) are thought to play a central role in the pathogenesis of chronic inflammatory diseases and non-Hodgkin's lymphomas is discussed.
PubMedExpression of a human homing receptor (CD44) in lymphoid malignancies and related stages of lymphoid development.
84 Citations1990E Horst, C J Meijer +6 more
It was found that CD44 exhibits a trimodal distribution on developing lymphocytes of both the T and B lineage that closely matches the recirculatory versus sessile nature of lymphoid cells at consecutive phases of their development, and thus apparently reflects its homing receptor function.
PubMedInvasiveness of T-cell hybridomas in vitro and their metastatic potential in vivo.
62 Citations1985Ed Roos, G. La Rivière +3 more
Property derived from normal T-cells, when introduced into noninvasive T-lymphoma cells, cause them to become invasive as well as metastatic, and for this tumor cell type invasiveness appears to be closely associated with the ability to colonize organs from the bloodstream.
Structure, Function, and Regulation of Molecules Involved in Leukocyte Adhesion
43 Citations1993Peter E. Lipsky, Robert Rothlein +2 more
NatureProduction of Self-directed Antibody by Tumour Cells
7 Citations1968Jesse Charney
These studies were designed to determine whether Rous sarcoma and other tumour cells have the capacity to produce self-directed antibody in vitro.