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. 1996 Feb;148(2):453–463.

Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation.

H J Terpe 1, S Störkel 1, U Zimmer 1, V Anquez 1, C Fischer 1, K Pantel 1, U Günthert 1
PMCID: PMC1861693  PMID: 8579108

Abstract

CD44 isoforms have been implicated in tumor progression and embryogenesis. Primary renal cell tumors (n = 100) of various histopathological differentiation and grading stages were analyzed for expression of CD44 isoforms in comparison with nonmalignant adult and fetal renal tissues. Evaluations were performed by immunohistochemistry using CD44 isoform-specific monoclonal antibodies and by reverse transcriptase polymerase chain reactions (RT-PCR). In the nonmalignant kidney no CD44 variant isoforms were detected. There was a significant increase in expression of CD44 standard (CD44s) and several variant isoforms (CD44v) in the course of tumor differentiation in clear cell carcinomas (n = 68) from stages G1 to G3 (P < 0.0001 for CD44s and isoforms containing CD44-6v, and P < 0.007 for those containing CD44-9v). Also, in chromophilic cell carcinomas (n = 13), CD44 isoform expression correlated with grading; ie, no CD44 expression was detected in G1 tumors, whereas in approximately 50% of the G2 tumors, CD44s, CD44-6v, and CD44-9v isoforms were present. Oncocytomas (n = 8), which are benign renal cell tumors, did not express CD44 isoforms, whereas invasive chromophobe cell carcinomas (n = 11) were positive for CD44s and CD44v isoforms. Transcript analyses by RT-PCR revealed that the upregulated isoforms in the carcinoma cells contained exons 8 to 10 and 3, 8 to 10 in combination from the variant region. In conclusion, expression of variant CD44 isoforms was strongly correlated with grading and appears to mediate a more aggressive phenotype to renal cell tumors.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  3. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  4. Dall P., Heider K. H., Sinn H. P., Skroch-Angel P., Adolf G., Kaufmann M., Herrlich P., Ponta H. Comparison of immunohistochemistry and RT-PCR for detection of CD44v-expression, a new prognostic factor in human breast cancer. Int J Cancer. 1995 Feb 8;60(4):471–477. doi: 10.1002/ijc.2910600408. [DOI] [PubMed] [Google Scholar]
  5. Droz D., Patey N., Paraf F., Chrétien Y., Gogusev J. Composition of extracellular matrix and distribution of cell adhesion molecules in renal cell tumors. Lab Invest. 1994 Nov;71(5):710–718. [PubMed] [Google Scholar]
  6. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Fujimoto K., Ichimori Y., Kakizoe T., Okajima E., Sakamoto H., Sugimura T., Terada M. Increased serum levels of basic fibroblast growth factor in patients with renal cell carcinoma. Biochem Biophys Res Commun. 1991 Oct 15;180(1):386–392. doi: 10.1016/s0006-291x(05)81305-1. [DOI] [PubMed] [Google Scholar]
  9. Gerharz C. D., Moll R., Störkel S., Ramp U., Thoenes W., Gabbert H. E. Ultrastructural appearance and cytoskeletal architecture of the clear, chromophilic, and chromophobe types of human renal cell carcinoma in vitro. Am J Pathol. 1993 Mar;142(3):851–859. [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. 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]
  12. Günthert U., Stauder R., Mayer B., Terpe H. J., Finke L., Friedrichs K. Are CD44 variant isoforms involved in human tumour progression? Cancer Surv. 1995;24:19–42. [PubMed] [Google Scholar]
  13. Jackson D. G., Bell J. I., Dickinson R., Timans J., Shields J., Whittle N. Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon. J Cell Biol. 1995 Feb;128(4):673–685. doi: 10.1083/jcb.128.4.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kovacs A., Storkel S., Thoenes W., Kovacs G. Mitochondrial and chromosomal DNA alterations in human chromophobe renal cell carcinomas. J Pathol. 1992 Jul;167(3):273–277. doi: 10.1002/path.1711670303. [DOI] [PubMed] [Google Scholar]
  15. Kovacs G. Molecular cytogenetics of renal cell tumors. Adv Cancer Res. 1993;62:89–124. doi: 10.1016/s0065-230x(08)60316-4. [DOI] [PubMed] [Google Scholar]
  16. Kovacs G. Molecular differential pathology of renal cell tumours. Histopathology. 1993 Jan;22(1):1–8. doi: 10.1111/j.1365-2559.1993.tb00061.x. [DOI] [PubMed] [Google Scholar]
  17. Kovacs G. The value of molecular genetic analysis in the diagnosis and prognosis of renal cell tumours. World J Urol. 1994;12(2):64–68. doi: 10.1007/BF00184238. [DOI] [PubMed] [Google Scholar]
  18. Lubinski J., Hadaczek P., Podolski J., Toloczko A., Sikorski A., McCue P., Druck T., Huebner K. Common regions of deletion in chromosome regions 3p12 and 3p14.2 in primary clear cell renal carcinomas. Cancer Res. 1994 Jul 15;54(14):3710–3713. [PubMed] [Google Scholar]
  19. 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]
  20. Nanus D. M., Schmitz-Dräger B. J., Motzer R. J., Lee A. C., Vlamis V., Cordon-Cardo C., Albino A. P., Reuter V. E. Expression of basic fibroblast growth factor in primary human renal tumors: correlation with poor survival. J Natl Cancer Inst. 1993 Oct 6;85(19):1597–1599. doi: 10.1093/jnci/85.19.1597. [DOI] [PubMed] [Google Scholar]
  21. Pantel K., Schlimok G., Braun S., Kutter D., Lindemann F., Schaller G., Funke I., Izbicki J. R., Riethmüller G. Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. J Natl Cancer Inst. 1993 Sep 1;85(17):1419–1424. doi: 10.1093/jnci/85.17.1419. [DOI] [PubMed] [Google Scholar]
  22. Rotter M., Block T., Busch R., Thanner S., Höfler H. Expression of HER-2/neu in renal-cell carcinoma. Correlation with histologic subtypes and differentiation. Int J Cancer. 1992 Sep 9;52(2):213–217. doi: 10.1002/ijc.2910520210. [DOI] [PubMed] [Google Scholar]
  23. Ruiz P., Schwärzler C., Günthert U. CD44 isoforms during differentiation and development. Bioessays. 1995 Jan;17(1):17–24. doi: 10.1002/bies.950170106. [DOI] [PubMed] [Google Scholar]
  24. Screaton G. R., Bell M. V., Bell J. I., Jackson D. G. The identification of a new alternative exon with highly restricted tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. Comparison of all 10 variable exons between mouse, human, and rat. J Biol Chem. 1993 Jun 15;268(17):12235–12238. [PubMed] [Google Scholar]
  25. 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]
  26. Stauder R., Eisterer W., Thaler J., Günthert U. CD44 variant isoforms in non-Hodgkin's lymphoma: a new independent prognostic factor. Blood. 1995 May 15;85(10):2885–2899. [PubMed] [Google Scholar]
  27. Strohmeyer T. G., Slamon D. J. Proto-oncogenes and tumor suppressor genes in human urological malignancies. J Urol. 1994 Jun;151(6):1479–1497. doi: 10.1016/s0022-5347(17)35284-9. [DOI] [PubMed] [Google Scholar]
  28. Störkel S. Karzinome und Onkozytome der Niere. Phänotypische Charakterisierung und prognostische Merkmale. Veroff Pathol. 1993;140:1–165. [PubMed] [Google Scholar]
  29. Störkel S., Keymer R., Steinbach F., Thoenes W. Reaction patterns of tumor infiltrating lymphocytes in different renal cell carcinomas and oncocytomas. Prog Clin Biol Res. 1992;378:217–223. [PubMed] [Google Scholar]
  30. Terpe H. J., Stark H., Prehm P., Günthert U. CD44 variant isoforms are preferentially expressed in basal epithelial of non-malignant human fetal and adult tissues. Histochemistry. 1994 Feb;101(2):79–89. doi: 10.1007/BF00269353. [DOI] [PubMed] [Google Scholar]
  31. Terpe H. J., Tajrobehkar K., Günthert U., Altmannsberger M. Expression of cell adhesion molecules alpha-2, alpha-5 and alpha-6 integrin, E-cadherin, N-CAM and CD-44 in renal cell carcinomas. An immunohistochemical study. Virchows Arch A Pathol Anat Histopathol. 1993;422(3):219–224. doi: 10.1007/BF01621805. [DOI] [PubMed] [Google Scholar]
  32. Thoenes W., Störkel S., Rumpelt H. J. Histopathology and classification of renal cell tumors (adenomas, oncocytomas and carcinomas). The basic cytological and histopathological elements and their use for diagnostics. Pathol Res Pract. 1986 May;181(2):125–143. doi: 10.1016/S0344-0338(86)80001-2. [DOI] [PubMed] [Google Scholar]
  33. Uchida T., Wada C., Wang C., Egawa S., Ohtani H., Koshiba K. Genomic instability of microsatellite repeats and mutations of H-, K-, and N-ras, and p53 genes in renal cell carcinoma. Cancer Res. 1994 Jul 15;54(14):3682–3685. [PubMed] [Google Scholar]
  34. van den Berg E., van der Hout A. H., Oosterhuis J. W., Störkel S., Dijkhuizen T., Dam A., Zweers H. M., Mensink H. J., Buys C. H., de Jong B. Cytogenetic analysis of epithelial renal-cell tumors: relationship with a new histopathological classification. Int J Cancer. 1993 Sep 9;55(2):223–227. doi: 10.1002/ijc.2910550210. [DOI] [PubMed] [Google Scholar]
  35. van der Poel H. G., Mulders P. F., Oosterhof G. O., Schaafsma H. E., Hendriks J. C., Schalken J. A., Debruyne F. M. Prognostic value of karyometric and clinical characteristics in renal cell carcinoma. Quantitative assessment of tumor heterogeneity. Cancer. 1993 Nov 1;72(9):2667–2674. doi: 10.1002/1097-0142(19931101)72:9<2667::aid-cncr2820720924>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]

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