Abstract
CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and might be a determinant of metastatic and invasive behaviour in carcinomas. The generation of CD44 splice variants might be linked closely with gastric carcinoma tumorigenesis and differentiation. Some studies have reported that the magnitude of CD44 variant synthesis at the protein level correlates with lymph node metastasis. A number of studies have examined the possible mechanism of involvement of the CD44 variant in tumour metastasis. Most studies have reported that the regulation of CD44 binding to hyaluronate results from glycosylation of variably spliced exons. Direct hyaluronate binding studies of CD44 V4-V7 isoforms transfected into the human gastric carcinoma cell line, SC-M1, have indicated that the V4-V7 isoforms themselves, in addition to glycosylation, can alter hyaluronate binding.
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- 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]
- Bargatze R. F., Wu N. W., Weissman I. L., Butcher E. C. High endothelial venule binding as a predictor of the dissemination of passaged murine lymphomas. J Exp Med. 1987 Oct 1;166(4):1125–1131. doi: 10.1084/jem.166.4.1125. [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]
- Berg E. L., Goldstein L. A., Jutila M. A., Nakache M., Picker L. J., Streeter P. R., Wu N. W., Zhou D., Butcher E. C. Homing receptors and vascular addressins: cell adhesion molecules that direct lymphocyte traffic. Immunol Rev. 1989 Apr;108:5–18. doi: 10.1111/j.1600-065x.1989.tb00010.x. [DOI] [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]
- Combaret V., Gross N., Lasset C., Frappaz D., Peruisseau G., Philip T., Beck D., Favrot M. C. Clinical relevance of CD44 cell-surface expression and N-myc gene amplification in a multicentric analysis of 121 pediatric neuroblastomas. J Clin Oncol. 1996 Jan;14(1):25–34. doi: 10.1200/JCO.1996.14.1.25. [DOI] [PubMed] [Google Scholar]
- Deb T. B., Datta K. Molecular cloning of human fibroblast hyaluronic acid-binding protein confirms its identity with P-32, a protein co-purified with splicing factor SF2. Hyaluronic acid-binding protein as P-32 protein, co-purified with splicing factor SF2. J Biol Chem. 1996 Jan 26;271(4):2206–2212. doi: 10.1074/jbc.271.4.2206. [DOI] [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]
- 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]
- Goldstein L. A., Zhou D. F., Picker L. J., Minty C. N., Bargatze R. F., Ding J. F., Butcher E. C. A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell. 1989 Mar 24;56(6):1063–1072. doi: 10.1016/0092-8674(89)90639-9. [DOI] [PubMed] [Google Scholar]
- Guo Y. J., Liu G., Wang X., Jin D., Wu M., Ma J., Sy M. S. Potential use of soluble CD44 in serum as indicator of tumor burden and metastasis in patients with gastric or colon cancer. Cancer Res. 1994 Jan 15;54(2):422–426. [PubMed] [Google Scholar]
- Günthert U. CD44: a multitude of isoforms with diverse functions. Curr Top Microbiol Immunol. 1993;184:47–63. doi: 10.1007/978-3-642-78253-4_4. [DOI] [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]
- Harn H. J., Ho L. I., Chang J. Y., Wu C. W., Jiang S. Y., Lee H. S., Lee W. H. Differential expression of the human metastasis adhesion molecule CD44V in normal and carcinomatous stomach mucosa of Chinese subjects. Cancer. 1995 Mar 1;75(5):1065–1071. doi: 10.1002/1097-0142(19950301)75:5<1065::aid-cncr2820750503>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
- Harn H. J., Ho L. I., Shyu R. Y., Yuan J. S., Lin F. G., Young T. H., Liu C. A., Tang H. S., Lee W. H. Soluble CD44 isoforms in serum as potential markers of metastatic gastric carcinoma. J Clin Gastroenterol. 1996 Mar;22(2):107–110. doi: 10.1097/00004836-199603000-00006. [DOI] [PubMed] [Google Scholar]
- Harn H. J., Ho L. I., Yu C. P., Wang M. W., Lee H. S., Lin J. J., Lee W. H., Isola N. R., Cooper D. L. The variant mRNA isoform of human metastasis gene (CD44V) detected in the cell lines of human hepatocellular carcinoma. Biochem Mol Biol Int. 1994 Feb;32(2):233–238. [PubMed] [Google Scholar]
- Harn H. J., Shen K. L., Liu C. A., Ho L. I., Yang L. S., Yueh K. C. Hyaluronate binding assay study of transfected CD44 V4-V7 isoforms into the human gastric carcinoma cell line SC-M1. J Pathol. 1998 Mar;184(3):291–296. doi: 10.1002/(SICI)1096-9896(199803)184:3<291::AID-PATH1>3.0.CO;2-O. [DOI] [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., Dämmrich J., Skroch-Angel P., Müller-Hermelink H. K., Vollmers H. P., Herrlich P., Ponta H. Differential expression of CD44 splice variants in intestinal- and diffuse-type human gastric carcinomas and normal gastric mucosa. Cancer Res. 1993 Sep 15;53(18):4197–4203. [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]
- 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]
- Hong R. L., Lee W. J., Shun C. T., Chu J. S., Chen Y. C. Expression of CD44 and its clinical implication in diffuse-type and intestinal-type gastric adenocarcinomas. Oncology. 1995 Jul-Aug;52(4):334–339. doi: 10.1159/000227485. [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]
- 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]
- Jalkanen S., Reichert R. A., Gallatin W. M., Bargatze R. F., Weissman I. L., Butcher E. C. Homing receptors and the control of lymphocyte migration. Immunol Rev. 1986 Jun;91:39–60. doi: 10.1111/j.1600-065x.1986.tb01483.x. [DOI] [PubMed] [Google Scholar]
- Kainz C., Kohlberger P., Tempfer C., Sliutz G., Gitsch G., Reinthaller A., Breitenecker G. Prognostic value of CD44 splice variants in human stage III cervical cancer. Eur J Cancer. 1995 Sep;31A(10):1706–1709. doi: 10.1016/0959-8049(95)00353-k. [DOI] [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]
- Kimata K., Honma Y., Okayama M., Oguri K., Hozumi M., Suzuki S. Increased synthesis of hyaluronic acid by mouse mammary carcinoma cell variants with high metastatic potential. Cancer Res. 1983 Mar;43(3):1347–1354. [PubMed] [Google Scholar]
- Knudson W., Biswas C., Toole B. P. Stimulation of glycosaminoglycan production in murine tumors. J Cell Biochem. 1984;25(4):183–196. doi: 10.1002/jcb.240250402. [DOI] [PubMed] [Google Scholar]
- Konig H., Moll J., Ponta H., Herrlich P. Trans-acting factors regulate the expression of CD44 splice variants. EMBO J. 1996 Aug 1;15(15):4030–4039. [PMC free article] [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]
- Lesley J., English N., Perschl A., Gregoroff J., Hyman R. Variant cell lines selected for alterations in the function of the hyaluronan receptor CD44 show differences in glycosylation. J Exp Med. 1995 Aug 1;182(2):431–437. doi: 10.1084/jem.182.2.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Manten-Horst E., Danen E. H., Smit L., Snoek M., Le Poole I. C., Van Muijen G. N., Pals S. T., Ruiter D. J. Expression of CD44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential. Int J Cancer. 1995 Jun 22;64(3):182–188. doi: 10.1002/ijc.2910640307. [DOI] [PubMed] [Google Scholar]
- Matsumura Y., Tarin D. Significance of CD44 gene products for cancer diagnosis and disease evaluation. Lancet. 1992 Oct 31;340(8827):1053–1058. doi: 10.1016/0140-6736(92)93077-z. [DOI] [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]
- Picker L. J., Nakache M., Butcher E. C. Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types. J Cell Biol. 1989 Aug;109(2):927–937. doi: 10.1083/jcb.109.2.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salles G., Zain M., Jiang W. M., Boussiotis V. A., Shipp M. A. Alternatively spliced CD44 transcripts in diffuse large-cell lymphomas: characterization and comparison with normal activated B cells and epithelial malignancies. Blood. 1993 Dec 15;82(12):3539–3547. [PubMed] [Google Scholar]
- Screaton G. R., Bell M. V., Jackson D. G., Cornelis F. B., Gerth U., Bell J. I. Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160–12164. doi: 10.1073/pnas.89.24.12160. [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]
- Toole B. P., Biswas C., Gross J. Hyaluronate and invasiveness of the rabbit V2 carcinoma. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6299–6303. doi: 10.1073/pnas.76.12.6299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turley E. A., Tretiak M. Glycosaminoglycan production by murine melanoma variants in vivo and in vitro. Cancer Res. 1985 Oct;45(10):5098–5105. [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]
- Washington K., Gottfried M. R., Telen M. J. Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas. Hum Pathol. 1994 Oct;25(10):1043–1049. doi: 10.1016/0046-8177(94)90063-9. [DOI] [PubMed] [Google Scholar]