Abstract
Surgical specimens of the normal kidney and of renal cell carcinoma (RCC) tissues at different stages of progression and of various histological grades were examined for the expression of MUC1 mucins with sialylated carbohydrates (sialylated MUC1 mucins) using a monoclonal antibody MY.1E12. Immunohistochemical studies revealed that the binding sites for this antibody were localized to the apical side of the epithelial cells of the distal convoluted tubules, Henle's loops and collecting ducts. However, proximal convoluted tubules, where RCC is considered to originate, were not stained. This antibody also bound strongly to RCC at advanced stages of progression and at metastatic sites, and to RCC of histologically high grades (undifferentiated). The epitope, presumably sialylated MUC1 mucin, was detected not only along the surface of the cell membranes but also in the cytoplasm. The level of expression of sialylated MUC1 mucins was inversely correlated with the survival of the patients with RCC and the disease-free survival period after curative surgery. Western blot analysis demonstrated that the electrophoretic mobility of sialylated MUC1 mucins of RCC was greater than that from the normal kidney. It is suggested that high levels of expression of sialylated MUC1 mucins in certain human RCC populations correlate with the aggressiveness of the disease, such as the tendency to form metastasis. © 1999 Cancer Research Campaign
Keywords: renal cell carcinoma, metastasis, MUC1 mucin, prognosis
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- Agrawal B., Krantz M. J., Reddish M. A., Longenecker B. M. Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2. Nat Med. 1998 Jan;4(1):43–49. doi: 10.1038/nm0198-043. [DOI] [PubMed] [Google Scholar]
- Birchmeier W., Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1994 May 27;1198(1):11–26. doi: 10.1016/0304-419x(94)90003-5. [DOI] [PubMed] [Google Scholar]
- Dohi D. F., Sutton R. C., Frazier M. L., Nakamori S., McIsaac A. M., Irimura T. Regulation of sialomucin production in colon carcinoma cells. J Biol Chem. 1993 May 15;268(14):10133–10138. [PubMed] [Google Scholar]
- Fojo A. T., Ueda K., Slamon D. J., Poplack D. G., Gottesman M. M., Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A. 1987 Jan;84(1):265–269. doi: 10.1073/pnas.84.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gendler S. J., Lancaster C. A., Taylor-Papadimitriou J., Duhig T., Peat N., Burchell J., Pemberton L., Lalani E. N., Wilson D. Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. J Biol Chem. 1990 Sep 5;265(25):15286–15293. [PubMed] [Google Scholar]
- Gendler S. J., Spicer A. P. Epithelial mucin genes. Annu Rev Physiol. 1995;57:607–634. doi: 10.1146/annurev.ph.57.030195.003135. [DOI] [PubMed] [Google Scholar]
- Giberti C., Oneto F., Martorana G., Rovida S., Carmignani G. Radical nephrectomy for renal cell carcinoma: long-term results and prognostic factors on a series of 328 cases. Eur Urol. 1997;31(1):40–48. doi: 10.1159/000474416. [DOI] [PubMed] [Google Scholar]
- Gimmi C. D., Morrison B. W., Mainprice B. A., Gribben J. G., Boussiotis V. A., Freeman G. J., Park S. Y., Watanabe M., Gong J., Hayes D. F. Breast cancer-associated antigen, DF3/MUC1, induces apoptosis of activated human T cells. Nat Med. 1996 Dec;2(12):1367–1370. doi: 10.1038/nm1296-1367. [DOI] [PubMed] [Google Scholar]
- Hilkens J., Ligtenberg M. J., Vos H. L., Litvinov S. V. Cell membrane-associated mucins and their adhesion-modulating property. Trends Biochem Sci. 1992 Sep;17(9):359–363. doi: 10.1016/0968-0004(92)90315-z. [DOI] [PubMed] [Google Scholar]
- Holland J. M. Proceedings: Cancer of the kidney--natural history and staging. Cancer. 1973 Nov;32(5):1030–1042. doi: 10.1002/1097-0142(197311)32:5<1030::aid-cncr2820320502>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
- Irimura T., Matsushita Y., Hoff S. D., Yamori T., Nakamori S., Frazier M. L., Giacco G. G., Cleary K. R., Ota D. M. Ectopic expression of mucins in colorectal cancer metastasis. Semin Cancer Biol. 1991 Apr;2(2):129–139. [PubMed] [Google Scholar]
- Irimura T., McIsaac A. M., Carlson D. A., Yagita M., Grimm E. A., Menter D. G., Ota D. M., Clary K. R. Soluble factor in normal tissues that stimulates high-molecular-weight sialoglycoprotein production by human colon carcinoma cells. Cancer Res. 1990 Jun 1;50(11):3331–3338. [PubMed] [Google Scholar]
- Irimura T., Nakamori S., Matsushita Y., Taniuchi Y., Todoroki N., Tsuji T., Izumi Y., Kawamura Y., Hoff S. D., Cleary K. R. Colorectal cancer metastasis determined by carbohydrate-mediated cell adhesion: role of sialyl-LeX antigens. Semin Cancer Biol. 1993 Oct;4(5):319–324. [PubMed] [Google Scholar]
- Jentoft N. Why are proteins O-glycosylated? Trends Biochem Sci. 1990 Aug;15(8):291–294. doi: 10.1016/0968-0004(90)90014-3. [DOI] [PubMed] [Google Scholar]
- Katagiri A., Watanabe R., Tomita Y. E-cadherin expression in renal cell cancer and its significance in metastasis and survival. Br J Cancer. 1995 Feb;71(2):376–379. doi: 10.1038/bjc.1995.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lan M. S., Batra S. K., Qi W. N., Metzgar R. S., Hollingsworth M. A. Cloning and sequencing of a human pancreatic tumor mucin cDNA. J Biol Chem. 1990 Sep 5;265(25):15294–15299. [PubMed] [Google Scholar]
- Ligtenberg M. J., Buijs F., Vos H. L., Hilkens J. Suppression of cellular aggregation by high levels of episialin. Cancer Res. 1992 Apr 15;52(8):2318–2324. [PubMed] [Google Scholar]
- Litvinov S. V., Hilkens J. The epithelial sialomucin, episialin, is sialylated during recycling. J Biol Chem. 1993 Oct 5;268(28):21364–21371. [PubMed] [Google Scholar]
- Mackay B., Ordónez N. G., Khoursand J., Bennington J. L. The ultrastructure and immunocytochemistry of renal cell carcinoma. Ultrastruct Pathol. 1987;11(5-6):483–502. doi: 10.3109/01913128709048445. [DOI] [PubMed] [Google Scholar]
- Matsushita Y., Cleary K. R., Ota D. M., Hoff S. D., Irimura T. Sialyl-dimeric Lewis-X antigen expressed on mucin-like glycoproteins in colorectal cancer metastases. Lab Invest. 1990 Dec;63(6):780–791. [PubMed] [Google Scholar]
- Nakamori S., Ota D. M., Cleary K. R., Shirotani K., Irimura T. MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma. Gastroenterology. 1994 Feb;106(2):353–361. doi: 10.1016/0016-5085(94)90592-4. [DOI] [PubMed] [Google Scholar]
- Nicolson G. L. Cancer metastasis. Organ colonization and the cell-surface properties of malignant cells. Biochim Biophys Acta. 1982 Dec 21;695(2):113–176. doi: 10.1016/0304-419x(82)90020-8. [DOI] [PubMed] [Google Scholar]
- Oosterwijk E., Ruiter D. J., Wakka J. C., Huiskens-van der Meij J. W., Jonas U., Fleuren G. J., Zwartendijk J., Hoedemaeker P., Warnaar S. O. Immunohistochemical analysis of monoclonal antibodies to renal antigens. Application in the diagnosis of renal cell carcinoma. Am J Pathol. 1986 May;123(2):301–309. [PMC free article] [PubMed] [Google Scholar]
- Ponta H., Sleeman J., Herrlich P. Tumor metastasis formation: cell-surface proteins confer metastasis-promoting or -suppressing properties. Biochim Biophys Acta. 1994 May 27;1198(1):1–10. doi: 10.1016/0304-419x(94)90002-7. [DOI] [PubMed] [Google Scholar]
- Poste G., Fidler I. J. The pathogenesis of cancer metastasis. Nature. 1980 Jan 10;283(5743):139–146. doi: 10.1038/283139a0. [DOI] [PubMed] [Google Scholar]
- Sarna G., Figlin R., de Kernion J. Interferon in renal cell carcinoma. The UCLA experience. Cancer. 1987 Feb 1;59(3 Suppl):610–612. doi: 10.1002/1097-0142(19870201)59:3+<610::aid-cncr2820591306>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
- Shirotani K., Taylor-Papadimitriou J., Gendler S. J., Irimura T. Transcriptional regulation of the MUC1 mucin gene in colon carcinoma cells by a soluble factor. Identification of a regulatory element. J Biol Chem. 1994 May 27;269(21):15030–15035. [PubMed] [Google Scholar]
- Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science. 1991 Mar 22;251(5000):1451–1455. doi: 10.1126/science.2006419. [DOI] [PubMed] [Google Scholar]
- 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]
- Umeda T., Niijima T. Phase II study of alpha interferon on renal cell carcinoma. Summary of three collaborative trials. Cancer. 1986 Sep 15;58(6):1231–1235. doi: 10.1002/1097-0142(19860915)58:6<1231::aid-cncr2820580610>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Wesseling J., van der Valk S. W., Hilkens J. A mechanism for inhibition of E-cadherin-mediated cell-cell adhesion by the membrane-associated mucin episialin/MUC1. Mol Biol Cell. 1996 Apr;7(4):565–577. doi: 10.1091/mbc.7.4.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamamoto M., Bhavanandan V. P., Nakamori S., Irimura T. A novel monoclonal antibody specific for sialylated MUC1 mucin. Jpn J Cancer Res. 1996 May;87(5):488–496. doi: 10.1111/j.1349-7006.1996.tb00250.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van de Wiel-van Kemenade E., Ligtenberg M. J., de Boer A. J., Buijs F., Vos H. L., Melief C. J., Hilkens J., Figdor C. G. Episialin (MUC1) inhibits cytotoxic lymphocyte-target cell interaction. J Immunol. 1993 Jul 15;151(2):767–776. [PubMed] [Google Scholar]
- van der Werf-Messing B. Proceedings: Carcinoma of the kidney. Cancer. 1973 Nov;32(5):1056–1061. doi: 10.1002/1097-0142(197311)32:5<1056::aid-cncr2820320505>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
