{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T11:57:17Z","timestamp":1770983837157,"version":"3.50.1"},"reference-count":28,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[1995,4,1]],"date-time":"1995-04-01T00:00:00Z","timestamp":796694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>CD44 is a polymorphic cell surface glycoprotein, currently proposed to be the principal cell surface receptor for hyaluronan. However, different isoforms of CD44, expressed in human lymphoid tumor cells, appear to have distinct effects on the ability of the cells to attach to hyaluronan-coated surfaces and on their capacity to form tumors in vivo. In the present study, we address the mechanisms that may regulate CD44 isoform-dependent adhesion to hyaluronan. We use a human Burkitt lymphoma, stably transfected with six different alternatively spliced human CD44 isoforms, to determine their potential hyaluronan binding and tumor growth promoting roles. We show that transfectants expressing CD44 splice variants that contain variable exons 6-10, 7-10 and 8-10 adhere to hyaluronan-coated surfaces weakly and that corresponding tumor formation in vivo is delayed with respect to CD44-negative parental cell-derived tumors. Abundant shedding of these three isoforms may play a significant role in determining the rate of tumor development. Transfectants expressing variable exon 3, on the other hand, fail to display CD44-mediated adhesion to hyaluronan, but form bone marrow tumors rapidly following intravenous injection. These observations suggest that different mechanisms regulate CD44-mediated adhesion and tumor growth, and provide evidence that expression of exon v3 may confer novel ligand-binding properties.<\/jats:p>","DOI":"10.1242\/jcs.108.4.1723","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T16:25:31Z","timestamp":1619367931000},"page":"1723-1733","source":"Crossref","is-referenced-by-count":61,"title":["Regulation of growth and dissemination of a human lymphoma by CD44 splice variants"],"prefix":"10.1242","volume":"108","author":[{"given":"Armando","family":"Bartolazzi","sequence":"first","affiliation":[{"name":"1 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, and Pathology Research, MGH East, Building 149, 13th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Jackson","sequence":"additional","affiliation":[{"name":"2 Molecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Bennett","sequence":"additional","affiliation":[{"name":"3 Bristol-Myers Pharmaceutical Research Institute, First Avenue Seattle, WA 98121, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Aruffo","sequence":"additional","affiliation":[{"name":"3 Bristol-Myers Pharmaceutical Research Institute, First Avenue Seattle, WA 98121, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Dickinson","sequence":"additional","affiliation":[{"name":"4 Cantab Pharmaceuticals Ltd, Cambridge CB4 4GN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Shields","sequence":"additional","affiliation":[{"name":"4 Cantab Pharmaceuticals Ltd, Cambridge CB4 4GN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Whittle","sequence":"additional","affiliation":[{"name":"4 Cantab Pharmaceuticals Ltd, Cambridge CB4 4GN, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Stamenkovic","sequence":"additional","affiliation":[{"name":"1 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, and Pathology Research, MGH East, Building 149, 13th Street, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1995,4,1]]},"reference":[{"key":"2023122401142864000_JOCES_108_4_1723C1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1242\/jcs.87.1.133","article-title":"Isolation and culture of high endothelial cells from rat lymph node","volume":"87","author":"Ager","year":"1987","journal-title":"J. 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Immunol"},{"key":"2023122401142864000_JOCES_108_4_1723C5","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1083\/jcb.113.1.207","article-title":"Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons","volume":"113","author":"Brown","year":"1991","journal-title":"J. Cell Biol"},{"key":"2023122401142864000_JOCES_108_4_1723C6","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.1016\/S0021-9258(18)68908-2","article-title":"Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleated human cells","volume":"263","author":"Carter","year":"1988","journal-title":"J. Biol. 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Cell Biol"},{"key":"2023122401142864000_JOCES_108_4_1723C12","first-page":"5292","article-title":"CD44 splice variants confer metastatic behaviour in rats: homologous sequences are expressed in human tumor cell lines","volume":"51","author":"Hofmann","year":"1991","journal-title":"Cancer Res"},{"key":"2023122401142864000_JOCES_108_4_1723C13","doi-asserted-by":"crossref","first-page":"798","DOI":"10.4049\/jimmunol.143.3.798","article-title":"CD44 contributes to T cell activation","volume":"143","author":"Huet","year":"1989","journal-title":"J. Immunol"},{"key":"2023122401142864000_JOCES_108_4_1723C14","doi-asserted-by":"crossref","first-page":"4732","DOI":"10.1016\/S0021-9258(18)42893-1","article-title":"Multiple variants of the human lymphocyte homing receptor CD44 generated by insertions at a single site in the extracellular domain","volume":"267","author":"Jackson","year":"1992","journal-title":"J. Biol. 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