Abstract
CD44 is a transmembrane glycoprotein, the variant isoforms of which are coded for by alternative splicing, with the most prolific isoform being CD44 standard. CD44 is found in a wide variety of tissues including the central nervous system, lung, epidermis, liver, and pancreas, whereas variant isoforms of CD44 (CD44v) appear to have a much more restricted distribution. Variants of CD44 are expressed in tissues during development, including embryonic epithelia. Known functions of CD44 are cellular adhesion (aggregation and migration), hyaluronate degradation, lymphocyte activation, lymph node homing, myelopoiesis and lymphopoiesis, angiogenesis, and release of cytokines. The functions of CD44 are principally dependant on cellular adhesion in one setting or another. The role of CD44 in neoplasia is less well defined, although metastatic potential can be conferred on non-metastasising cell lines by transfection with a variant of CD44 and high levels of CD44 are associated with several types of malignant tumours. The physiological functions of CD44 indicate that the molecule could be involved in the metastatic spread of tumours. Many studies have investigated the pattern of CD44 distribution in tumours and some observations suggest that certain cells do not use CD44 in tumorigenesis or in the production of metastases. However, the data are extremely conflicting, and further studies are needed to establish the prognostic value of CD44 and its variant isoforms. The precise function of CD44 in the metastatic process and the degree of involvement in human malignancies has yet to be established fully.
Full Text
The Full Text of this article is available as a PDF (204.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alho A. M., Underhill C. B. The hyaluronate receptor is preferentially expressed on proliferating epithelial cells. J Cell Biol. 1989 Apr;108(4):1557–1565. doi: 10.1083/jcb.108.4.1557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arch R., Wirth K., Hofmann M., Ponta H., Matzku S., Herrlich P., Zöller M. Participation in normal immune responses of a metastasis-inducing splice variant of CD44. Science. 1992 Jul 31;257(5070):682–685. doi: 10.1126/science.1496383. [DOI] [PubMed] [Google Scholar]
- Aruffo A., Stamenkovic I., Melnick M., Underhill C. B., Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. doi: 10.1016/0092-8674(90)90694-a. [DOI] [PubMed] [Google Scholar]
- Bartolazzi A., Peach R., Aruffo A., Stamenkovic I. Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development. J Exp Med. 1994 Jul 1;180(1):53–66. doi: 10.1084/jem.180.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bennett K. L., Jackson D. G., Simon J. C., Tanczos E., Peach R., Modrell B., Stamenkovic I., Plowman G., Aruffo A. CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor. J Cell Biol. 1995 Feb;128(4):687–698. doi: 10.1083/jcb.128.4.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bennett K. L., Modrell B., Greenfield B., Bartolazzi A., Stamenkovic I., Peach R., Jackson D. G., Spring F., Aruffo A. Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons. J Cell Biol. 1995 Dec;131(6 Pt 1):1623–1633. doi: 10.1083/jcb.131.6.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bourguignon L. Y., Lokeshwar V. B., Chen X., Kerrick W. G. Hyaluronic acid-induced lymphocyte signal transduction and HA receptor (GP85/CD44)-cytoskeleton interaction. J Immunol. 1993 Dec 15;151(12):6634–6644. [PubMed] [Google Scholar]
- Brown T. A., Bouchard T., St John T., Wayner E., Carter W. G. Human keratinocytes express a new CD44 core protein (CD44E) as a heparan-sulfate intrinsic membrane proteoglycan with additional exons. J Cell Biol. 1991 Apr;113(1):207–221. doi: 10.1083/jcb.113.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carter W. G., Wayner E. A. Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleated human cells. J Biol Chem. 1988 Mar 25;263(9):4193–4201. [PubMed] [Google Scholar]
- Charpin C., Garcia S., Bouvier C., Devictor B., Andrac L., Choux R., Lavaut M. N., Allasia C. Automated and quantitative immunocytochemical assays of CD44v6 in breast carcinomas. Hum Pathol. 1997 Mar;28(3):289–296. doi: 10.1016/s0046-8177(97)90126-x. [DOI] [PubMed] [Google Scholar]
- Colón-Teicher L., Wise L. S., Martino J. J., Baskin L., Sakoulas G., Pollack R. E., Chen S. Genomic sequences capable of committing mouse and rat fibroblasts to adipogenesis. Nucleic Acids Res. 1993 May 11;21(9):2223–2228. doi: 10.1093/nar/21.9.2223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Conrad P., Rothman B. L., Kelley K. A., Blue M. L. Mechanism of peripheral T cell activation by coengagement of CD44 and CD2. J Immunol. 1992 Sep 15;149(6):1833–1839. [PubMed] [Google Scholar]
- Cooper D. L., Dougherty G. J. To metastasize or not? Selection of CD44 splice sites. Nat Med. 1995 Jul;1(7):635–637. doi: 10.1038/nm0795-635. [DOI] [PubMed] [Google Scholar]
- Cooper D. L., Dougherty G., Harn H. J., Jackson S., Baptist E. W., Byers J., Datta A., Phillips G., Isola N. R. The complex CD44 transcriptional unit; alternative splicing of three internal exons generates the epithelial form of CD44. Biochem Biophys Res Commun. 1992 Jan 31;182(2):569–578. doi: 10.1016/0006-291x(92)91770-q. [DOI] [PubMed] [Google Scholar]
- Culty M., Shizari M., Thompson E. W., Underhill C. B. Binding and degradation of hyaluronan by human breast cancer cell lines expressing different forms of CD44: correlation with invasive potential. J Cell Physiol. 1994 Aug;160(2):275–286. doi: 10.1002/jcp.1041600209. [DOI] [PubMed] [Google Scholar]
- Dall P., Hekele A., Ikenberg H., Göppinger A., Bauknecht T., Pfleiderer A., Moll J., Hofmann M., Ponta H., Herrlich P. Increasing incidence of CD44v7/8 epitope expression during uterine cervical carcinogenesis. Int J Cancer. 1996 Apr 22;69(2):79–85. doi: 10.1002/(SICI)1097-0215(19960422)69:2<79::AID-IJC2>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
- Danen E. H., ten Berge P. J., van Muijen G. N., Jager M. J., Ruiter D. J. Expression of CD44 and the pattern of CD44 alternative splicing in uveal melanoma. Melanoma Res. 1996 Feb;6(1):31–35. doi: 10.1097/00008390-199602000-00005. [DOI] [PubMed] [Google Scholar]
- De Rossi G., Marroni P., Paganuzzi M., Mauro F. R., Tenca C., Zarcone D., Velardi A., Molica S., Grossi C. E. Increased serum levels of soluble CD44 standard, but not of variant isoforms v5 and v6, in B cell chronic lymphocytic leukemia. Leukemia. 1997 Jan;11(1):134–141. doi: 10.1038/sj.leu.2400525. [DOI] [PubMed] [Google Scholar]
- Dämmrich J., Vollmers H. P., Heider K. H., Müller-Hermelink H. K. Importance of different CD44v6 expression in human gastric intestinal and diffuse type cancers for metastatic lymphogenic spreading. J Mol Med (Berl) 1995 Aug;73(8):395–401. doi: 10.1007/BF00240138. [DOI] [PubMed] [Google Scholar]
- Ermak G., Jennings T., Robinson L., Ross J. S., Figge J. Restricted patterns of CD44 variant exon expression in human papillary thyroid carcinoma. Cancer Res. 1996 Mar 1;56(5):1037–1042. [PubMed] [Google Scholar]
- Faassen A. E., Schrager J. A., Klein D. J., Oegema T. R., Couchman J. R., McCarthy J. B. A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion. J Cell Biol. 1992 Jan;116(2):521–531. doi: 10.1083/jcb.116.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fox S. B., Fawcett J., Jackson D. G., Collins I., Gatter K. C., Harris A. L., Gearing A., Simmons D. L. Normal human tissues, in addition to some tumors, express multiple different CD44 isoforms. Cancer Res. 1994 Aug 15;54(16):4539–4546. [PubMed] [Google Scholar]
- Fox S. B., Gatter K. C., Jackson D. G., Screaton G. R., Bell M. V., Bell J. I., Harris A. L., Simmons D., Fawcett J. CD44 and cancer screening. Lancet. 1993 Aug 28;342(8870):548–549. doi: 10.1016/0140-6736(93)91670-h. [DOI] [PubMed] [Google Scholar]
- Friedrichs K., Franke F., Lisboa B. W., Kügler G., Gille I., Terpe H. J., Hölzel F., Maass H., Günthert U. CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. Cancer Res. 1995 Nov 15;55(22):5424–5433. [PubMed] [Google Scholar]
- Gallagher J. T. The protein and proteoglycan guises of Hermes/CD44. Glycobiology. 1992 Apr;2(2):93–94. doi: 10.1093/glycob/2.2.93. [DOI] [PubMed] [Google Scholar]
- Gansauge F., Gansauge S., Zobywalski A., Scharnweber C., Link K. H., Nussler A. K., Beger H. G. Differential expression of CD44 splice variants in human pancreatic adenocarcinoma and in normal pancreas. Cancer Res. 1995 Dec 1;55(23):5499–5503. [PubMed] [Google Scholar]
- Gao A. C., Lou W., Dong J. T., Isaacs J. T. CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. Cancer Res. 1997 Mar 1;57(5):846–849. [PubMed] [Google Scholar]
- Givehchian M., Woerner S. M., Lacroix J., Zöller M., Drings P., Becker H., Kayser K., Ridder R., von Knebel Doeberitz M. Expression of CD44 splice variants in normal respiratory epithelium and bronchial carcinomas: no evidence for altered CD44 splicing in metastasis. Oncogene. 1996 Mar 7;12(5):1137–1144. [PubMed] [Google Scholar]
- Goldstein L. A., Butcher E. C. Identification of mRNA that encodes an alternative form of H-CAM(CD44) in lymphoid and nonlymphoid tissues. Immunogenetics. 1990;32(6):389–397. doi: 10.1007/BF00241632. [DOI] [PubMed] [Google Scholar]
- Goodfellow P. N., Banting G., Wiles M. V., Tunnacliffe A., Parkar M., Solomon E., Dalchau R., Fabre J. W. The gene, MIC4, which controls expression of the antigen defined by monoclonal antibody F10.44.2, is on human chromosome 11. Eur J Immunol. 1982 Aug;12(8):659–663. doi: 10.1002/eji.1830120807. [DOI] [PubMed] [Google Scholar]
- Green S. J., Tarone G., Underhill C. B. Aggregation of macrophages and fibroblasts is inhibited by a monoclonal antibody to the hyaluronate receptor. Exp Cell Res. 1988 Oct;178(2):224–232. doi: 10.1016/0014-4827(88)90393-x. [DOI] [PubMed] [Google Scholar]
- Guo Y., Ma J., Wang J., Che X., Narula J., Bigby M., Wu M., Sy M. S. Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res. 1994 Mar 15;54(6):1561–1565. [PubMed] [Google Scholar]
- Günthert U., Hofmann M., Rudy W., Reber S., Zöller M., Haussmann I., Matzku S., Wenzel A., Ponta H., Herrlich P. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991 Apr 5;65(1):13–24. doi: 10.1016/0092-8674(91)90403-l. [DOI] [PubMed] [Google Scholar]
- Hardingham T. E., Fosang A. J. Proteoglycans: many forms and many functions. FASEB J. 1992 Feb 1;6(3):861–870. [PubMed] [Google Scholar]
- Haynes B. F., Liao H. X., Patton K. L. The transmembrane hyaluronate receptor (CD44): multiple functions, multiple forms. Cancer Cells. 1991 Sep;3(9):347–350. [PubMed] [Google Scholar]
- Haynes B. F., Telen M. J., Hale L. P., Denning S. M. CD44--a molecule involved in leukocyte adherence and T-cell activation. Immunol Today. 1989 Dec;10(12):423–428. doi: 10.1016/0167-5699(89)90040-6. [DOI] [PubMed] [Google Scholar]
- Heider K. H., Hofmann M., Hors E., van den Berg F., Ponta H., Herrlich P., Pals S. T. A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps. J Cell Biol. 1993 Jan;120(1):227–233. doi: 10.1083/jcb.120.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Higashikawa K., Yokozaki H., Ue T., Taniyama K., Ishikawa T., Tarin D., Tahara E. Evaluation of CD44 transcription variants in human digestive tract carcinomas and normal tissues. Int J Cancer. 1996 Mar 28;66(1):11–17. doi: 10.1002/(SICI)1097-0215(19960328)66:1<11::AID-IJC3>3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
- Hofmann M., Rudy W., Günthert U., Zimmer S. G., Zawadzki V., Zöller M., Lichtner R. B., Herrlich P., Ponta H. A 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. Cancer Res. 1993 Apr 1;53(7):1516–1521. [PubMed] [Google Scholar]
- Hofmann M., Rudy W., Zöller M., Tölg C., Ponta H., Herrlich P., Günthert U. CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines. Cancer Res. 1991 Oct 1;51(19):5292–5297. [PubMed] [Google Scholar]
- Horst E., Meijer C. J., Radaszkiewicz T., Ossekoppele G. J., Van Krieken J. H., Pals S. T. Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54). Leukemia. 1990 Aug;4(8):595–599. [PubMed] [Google Scholar]
- Hudson D. L., Speight P. M., Watt F. M. Altered expression of CD44 isoforms in squamous-cell carcinomas and cell lines derived from them. Int J Cancer. 1996 May 16;66(4):457–463. doi: 10.1002/(SICI)1097-0215(19960516)66:4<457::AID-IJC8>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
- Huet S., Groux H., Caillou B., Valentin H., Prieur A. M., Bernard A. CD44 contributes to T cell activation. J Immunol. 1989 Aug 1;143(3):798–801. [PubMed] [Google Scholar]
- Hughes E. N., Mengod G., August J. T. Murine cell surface glycoproteins. Characterization of a major component of 80,000 daltons as a polymorphic differentiation antigen of mesenchymal cells. J Biol Chem. 1981 Jul 10;256(13):7023–7027. [PubMed] [Google Scholar]
- Idzerda R. L., Carter W. G., Nottenburg C., Wayner E. A., Gallatin W. M., St John T. Isolation and DNA sequence of a cDNA clone encoding a lymphocyte adhesion receptor for high endothelium. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4659–4663. doi: 10.1073/pnas.86.12.4659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jain M., He Q., Lee W. S., Kashiki S., Foster L. C., Tsai J. C., Lee M. E., Haber E. Role of CD44 in the reaction of vascular smooth muscle cells to arterial wall injury. J Clin Invest. 1996 Feb 1;97(3):596–603. doi: 10.1172/JCI118455. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jalkanen S. T., Bargatze R. F., Herron L. R., Butcher E. C. A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man. Eur J Immunol. 1986 Oct;16(10):1195–1202. doi: 10.1002/eji.1830161003. [DOI] [PubMed] [Google Scholar]
- Jalkanen S. T., Bargatze R. F., Herron L. R., Butcher E. C. A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man. Eur J Immunol. 1986 Oct;16(10):1195–1202. doi: 10.1002/eji.1830161003. [DOI] [PubMed] [Google Scholar]
- Jalkanen S., Bargatze R. F., de los Toyos J., Butcher E. C. Lymphocyte 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. J Cell Biol. 1987 Aug;105(2):983–990. doi: 10.1083/jcb.105.2.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jalkanen S., Jalkanen M., Bargatze R., Tammi M., Butcher E. C. Biochemical properties of glycoproteins involved in lymphocyte recognition of high endothelial venules in man. J Immunol. 1988 Sep 1;141(5):1615–1623. [PubMed] [Google Scholar]
- Jiang W. G. In-vitro models of cancer invasion and metastasis: recent developments. Eur J Surg Oncol. 1994 Aug;20(4):493–499. [PubMed] [Google Scholar]
- Katoh S., Zheng Z., Oritani K., Shimozato T., Kincade P. W. Glycosylation of CD44 negatively regulates its recognition of hyaluronan. J Exp Med. 1995 Aug 1;182(2):419–429. doi: 10.1084/jem.182.2.419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaufmann M., Heider K. H., Sinn H. P., von Minckwitz G., Ponta H., Herrlich P. CD44 variant exon epitopes in primary breast cancer and length of survival. Lancet. 1995 Mar 11;345(8950):615–619. doi: 10.1016/s0140-6736(95)90521-9. [DOI] [PubMed] [Google Scholar]
- Kincade P. W. Molecular interactions between stromal cells and B lymphocyte precursors. Semin Immunol. 1991 Nov;3(6):379–390. [PubMed] [Google Scholar]
- Koopman G., Heider K. H., Horst E., Adolf G. R., van den Berg F., Ponta H., Herrlich P., Pals S. T. Activated human lymphocytes and aggressive non-Hodgkin's lymphomas express a homologue of the rat metastasis-associated variant of CD44. J Exp Med. 1993 Apr 1;177(4):897–904. doi: 10.1084/jem.177.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korabiowska M., Brinck U., Hönig J., Mora O., Bartkowski S., Schauer A. CD-44: a marker of metastases of head and neck melanomas. In Vivo. 1995 May-Jun;9(3):253–256. [PubMed] [Google Scholar]
- Labarrière N., Piau J. P., Otry C., Denis M., Lustenberger P., Meflah K., Le Pendu J. H blood group antigen carried by CD44V modulates tumorigenicity of rat colon carcinoma cells. Cancer Res. 1994 Dec 1;54(23):6275–6281. [PubMed] [Google Scholar]
- Lees V. C., Fan T. P., West D. C. Angiogenesis in a delayed revascularization model is accelerated by angiogenic oligosaccharides of hyaluronan. Lab Invest. 1995 Aug;73(2):259–266. [PubMed] [Google Scholar]
- Lesley J., He Q., Miyake K., Hamann A., Hyman R., Kincade P. W. Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody. J Exp Med. 1992 Jan 1;175(1):257–266. doi: 10.1084/jem.175.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lesley J., Hyman R. CD44 can be activated to function as an hyaluronic acid receptor in normal murine T cells. Eur J Immunol. 1992 Oct;22(10):2719–2723. doi: 10.1002/eji.1830221036. [DOI] [PubMed] [Google Scholar]
- Lesley J., Kincade P. W., Hyman R. Antibody-induced activation of the hyaluronan receptor function of CD44 requires multivalent binding by antibody. Eur J Immunol. 1993 Aug;23(8):1902–1909. doi: 10.1002/eji.1830230826. [DOI] [PubMed] [Google Scholar]
- Lesley J., Schulte R., Hyman R. Binding of hyaluronic acid to lymphoid cell lines is inhibited by monoclonal antibodies against Pgp-1. Exp Cell Res. 1990 Apr;187(2):224–233. doi: 10.1016/0014-4827(90)90085-o. [DOI] [PubMed] [Google Scholar]
- Mackay C. R., Terpe H. J., Stauder R., Marston W. L., Stark H., Günthert U. Expression and modulation of CD44 variant isoforms in humans. J Cell Biol. 1994 Jan;124(1-2):71–82. doi: 10.1083/jcb.124.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayer B., Jauch K. W., Günthert U., Figdor C. G., Schildberg F. W., Funke I., Johnson J. P. De-novo expression of CD44 and survival in gastric cancer. Lancet. 1993 Oct 23;342(8878):1019–1022. doi: 10.1016/0140-6736(93)92879-x. [DOI] [PubMed] [Google Scholar]
- Miyake K., Medina K. L., Hayashi S., Ono S., Hamaoka T., Kincade P. W. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med. 1990 Feb 1;171(2):477–488. doi: 10.1084/jem.171.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller W., Schneiders A., Heider K. H., Meier S., Hommel G., Gabbert H. E. Expression and prognostic value of the CD44 splicing variants v5 and v6 in gastric cancer. J Pathol. 1997 Oct;183(2):222–227. doi: 10.1002/(SICI)1096-9896(199710)183:2<222::AID-PATH923>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
- Neame S. J., Isacke C. M. Phosphorylation of CD44 in vivo requires both Ser323 and Ser325, but does not regulate membrane localization or cytoskeletal interaction in epithelial cells. EMBO J. 1992 Dec;11(13):4733–4738. doi: 10.1002/j.1460-2075.1992.tb05578.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neame S. J., Isacke C. M. The cytoplasmic tail of CD44 is required for basolateral localization in epithelial MDCK cells but does not mediate association with the detergent-insoluble cytoskeleton of fibroblasts. J Cell Biol. 1993 Jun;121(6):1299–1310. doi: 10.1083/jcb.121.6.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nemec R. E., Toole B. P., Knudson W. The cell surface hyaluronate binding sites of invasive human bladder carcinoma cells. Biochem Biophys Res Commun. 1987 Nov 30;149(1):249–257. doi: 10.1016/0006-291x(87)91632-9. [DOI] [PubMed] [Google Scholar]
- Peach R. J., Hollenbaugh D., Stamenkovic I., Aruffo A. Identification of hyaluronic acid binding sites in the extracellular domain of CD44. J Cell Biol. 1993 Jul;122(1):257–264. doi: 10.1083/jcb.122.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pessac B., Defendi V. Cell aggregation: role of acid mucopolysaccharides. Science. 1972 Feb 25;175(4024):898–900. doi: 10.1126/science.175.4024.898. [DOI] [PubMed] [Google Scholar]
- Reber S., Matzku S., Günthert U., Ponta H., Herrlich P., Zöller M. Retardation of metastatic tumor growth after immunization with metastasis-specific monoclonal antibodies. Int J Cancer. 1990 Nov 15;46(5):919–927. doi: 10.1002/ijc.2910460528. [DOI] [PubMed] [Google Scholar]
- Reinholt F. P., Hultenby K., Oldberg A., Heinegård D. Osteopontin--a possible anchor of osteoclasts to bone. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4473–4475. doi: 10.1073/pnas.87.12.4473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salmi M., Grön-Virta K., Sointu P., Grenman R., Kalimo H., Jalkanen S. Regulated expression of exon v6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin. J Cell Biol. 1993 Jul;122(2):431–442. doi: 10.1083/jcb.122.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Satoh K., Shimosegawa T., Koizumi M., Toyota T. Expression of CD44 in duct cell carcinomas and in intraductal neoplasms of the pancreas. Anticancer Res. 1997 Jan-Feb;17(1A):215–219. [PubMed] [Google Scholar]
- Seiter S., Arch R., Reber S., Komitowski D., Hofmann M., Ponta H., Herrlich P., Matzku S., Zöller M. Prevention of tumor metastasis formation by anti-variant CD44. J Exp Med. 1993 Feb 1;177(2):443–455. doi: 10.1084/jem.177.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shimizu Y., Van Seventer G. A., Siraganian R., Wahl L., Shaw S. Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol. 1989 Oct 15;143(8):2457–2463. [PubMed] [Google Scholar]
- Singh R. P., Patarca R., Schwartz J., Singh P., Cantor H. Definition of a specific interaction between the early T lymphocyte activation 1 (Eta-1) protein and murine macrophages in vitro and its effect upon macrophages in vivo. J Exp Med. 1990 Jun 1;171(6):1931–1942. doi: 10.1084/jem.171.6.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sinn H. P., Heider K. H., Skroch-Angel P., von Minckwitz G., Kaufmann M., Herrlich P., Ponta H. Human mammary carcinomas express homologues of rat metastasis-associated variants of CD44. Breast Cancer Res Treat. 1995;36(3):307–313. doi: 10.1007/BF00713402. [DOI] [PubMed] [Google Scholar]
- Sleeman J., Moll J., Sherman L., Dall P., Pals S. T., Ponta H., Herrlich P. The role of CD44 splice variants in human metastatic cancer. Ciba Found Symp. 1995;189:142-51; discussion 151-6, 174-6. doi: 10.1002/9780470514719.ch11. [DOI] [PubMed] [Google Scholar]
- Sliutz G., Tempfer C., Winkler S., Kohlberger P., Reinthaller A., Kainz C. Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer. Br J Cancer. 1995 Dec;72(6):1494–1497. doi: 10.1038/bjc.1995.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stamenkovic I., Amiot M., Pesando J. M., Seed B. A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell. 1989 Mar 24;56(6):1057–1062. doi: 10.1016/0092-8674(89)90638-7. [DOI] [PubMed] [Google Scholar]
- Stamenkovic I., Aruffo A., Amiot M., Seed B. The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells. EMBO J. 1991 Feb;10(2):343–348. doi: 10.1002/j.1460-2075.1991.tb07955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stevens J. W., Palechek P. L., Griebling T. L., Midura R. J., Rokhlin O. W., Cohen M. B. Expression of CD44 isoforms in human prostate tumor cell lines. Prostate. 1996 Mar;28(3):153–161. doi: 10.1002/(SICI)1097-0045(199603)28:3<153::AID-PROS2>3.0.CO;2-G. [DOI] [PubMed] [Google Scholar]
- Takahashi K., Stamenkovic I., Cutler M., Saya H., Tanabe K. K. CD44 hyaluronate binding influences growth kinetics and tumorigenicity of human colon carcinomas. Oncogene. 1995 Dec 7;11(11):2223–2232. [PubMed] [Google Scholar]
- Trochon V., Mabilat C., Bertrand P., Legrand Y., Smadja-Joffe F., Soria C., Delpech B., Lu H. Evidence of involvement of CD44 in endothelial cell proliferation, migration and angiogenesis in vitro. Int J Cancer. 1996 May 29;66(5):664–668. doi: 10.1002/(SICI)1097-0215(19960529)66:5<664::AID-IJC14>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
- Trowbridge I. S., Lesley J., Schulte R., Hyman R., Trotter J. Biochemical characterization and cellular distribution of a polymorphic, murine cell-surface glycoprotein expressed on lymphoid tissues. Immunogenetics. 1982 Mar;15(3):299–312. doi: 10.1007/BF00364338. [DOI] [PubMed] [Google Scholar]
- Underhill C. B., Green S. J., Comoglio P. M., Tarone G. The hyaluronate receptor is identical to a glycoprotein of Mr 85,000 (gp85) as shown by a monoclonal antibody that interferes with binding activity. J Biol Chem. 1987 Sep 25;262(27):13142–13146. [PubMed] [Google Scholar]
- Underhill C. B. Interaction of hyaluronate with the surface of simian virus 40-transformed 3T3 cells: aggregation and binding studies. J Cell Sci. 1982 Aug;56:177–189. doi: 10.1242/jcs.56.1.177. [DOI] [PubMed] [Google Scholar]
- Underhill C. B., Toole B. P. Physical characteristics of hyaluronate binding to the surface of simian virus 40-transformed 3T3 cells. J Biol Chem. 1980 May 25;255(10):4544–4549. [PubMed] [Google Scholar]
- Underhill C. B., Toole B. P. Receptors for hyaluronate on the surface of parent and virus-transformed cell lines: binding and aggregation studies. Exp Cell Res. 1981 Feb;131(2):419–423. doi: 10.1016/0014-4827(81)90248-2. [DOI] [PubMed] [Google Scholar]
- Underhill C. CD44: the hyaluronan receptor. J Cell Sci. 1992 Oct;103(Pt 2):293–298. doi: 10.1242/jcs.103.2.293. [DOI] [PubMed] [Google Scholar]
- Underhill C., Dorfman A. The role of hyaluronic acid in intercellular adhesion of cultured mouse cells. Exp Cell Res. 1978 Nov;117(1):155–164. doi: 10.1016/0014-4827(78)90438-x. [DOI] [PubMed] [Google Scholar]
- Wayner E. A., Carter W. G. Identification of multiple cell adhesion receptors for collagen and fibronectin in human fibrosarcoma cells possessing unique alpha and common beta subunits. J Cell Biol. 1987 Oct;105(4):1873–1884. doi: 10.1083/jcb.105.4.1873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weber G. F., Ashkar S., Glimcher M. J., Cantor H. Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science. 1996 Jan 26;271(5248):509–512. doi: 10.1126/science.271.5248.509. [DOI] [PubMed] [Google Scholar]
- West D. C., Kumar S. The effect of hyaluronate and its oligosaccharides on endothelial cell proliferation and monolayer integrity. Exp Cell Res. 1989 Jul;183(1):179–196. doi: 10.1016/0014-4827(89)90428-x. [DOI] [PubMed] [Google Scholar]
- Wirth K., Arch R., Somasundaram C., Hofmann M., Weber B., Herrlich P., Matzku S., Zöller M. Expression of CD44 isoforms carrying metastasis-associated sequences in newborn and adult rats. Eur J Cancer. 1993;29A(8):1172–1177. doi: 10.1016/s0959-8049(05)80310-7. [DOI] [PubMed] [Google Scholar]
- Yamaguchi A., Saito M., Gio T., Iida A., Takeuchi K., Hirose K., Nakagawara G., Urano T., Furukawa K., Shiku H. Expression of CD44 variant exons 8-10 in gastric cancer. Jpn J Cancer Res. 1995 Dec;86(12):1166–1171. doi: 10.1111/j.1349-7006.1995.tb03310.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamaguchi A., Urano T., Goi T., Saito M., Takeuchi K., Hirose K., Nakagawara G., Shiku H., Furukawa K. Expression of a CD44 variant containing exons 8 to 10 is a useful independent factor for the prediction of prognosis in colorectal cancer patients. J Clin Oncol. 1996 Apr;14(4):1122–1127. doi: 10.1200/JCO.1996.14.4.1122. [DOI] [PubMed] [Google Scholar]
- Yanagishita M., Hascall V. C. Cell surface heparan sulfate proteoglycans. J Biol Chem. 1992 May 15;267(14):9451–9454. [PubMed] [Google Scholar]
- Yang B., Yang B. L., Savani R. C., Turley E. A. Identification of a common hyaluronan binding motif in the hyaluronan binding proteins RHAMM, CD44 and link protein. EMBO J. 1994 Jan 15;13(2):286–296. doi: 10.1002/j.1460-2075.1994.tb06261.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yu Q., Toole B. P. Common pattern of CD44 isoforms is expressed in morphogenetically active epithelia. Dev Dyn. 1997 Jan;208(1):1–10. doi: 10.1002/(SICI)1097-0177(199701)208:1<1::AID-AJA1>3.0.CO;2-M. [DOI] [PubMed] [Google Scholar]
- Yue T. L., McKenna P. J., Ohlstein E. H., Farach-Carson M. C., Butler W. T., Johanson K., McDevitt P., Feuerstein G. Z., Stadel J. M. Osteopontin-stimulated vascular smooth muscle cell migration is mediated by beta 3 integrin. Exp Cell Res. 1994 Oct;214(2):459–464. doi: 10.1006/excr.1994.1282. [DOI] [PubMed] [Google Scholar]
- Zahalka M. A., Okon E., Gosslar U., Holzmann B., Naor D. Lymph node (but not spleen) invasion by murine lymphoma is both CD44- and hyaluronate-dependent. J Immunol. 1995 May 15;154(10):5345–5355. [PubMed] [Google Scholar]
- Zetter B. R. Adhesion molecules in tumor metastasis. Semin Cancer Biol. 1993 Aug;4(4):219–229. [PubMed] [Google Scholar]
- Zigmond S. H. Cell locomotion and chemotaxis. Curr Opin Cell Biol. 1989 Feb;1(1):80–86. doi: 10.1016/s0955-0674(89)80041-9. [DOI] [PubMed] [Google Scholar]
- Zöller M. CD44: physiological expression of distinct isoforms as evidence for organ-specific metastasis formation. J Mol Med (Berl) 1995 Sep;73(9):425–438. doi: 10.1007/BF00202261. [DOI] [PubMed] [Google Scholar]
- van Weering D. H., Baas P. D., Bos J. L. A PCR-based method for the analysis of human CD44 splice products. PCR Methods Appl. 1993 Oct;3(2):100–106. doi: 10.1101/gr.3.2.100. [DOI] [PubMed] [Google Scholar]