Abstract
Ovarian adenocarcinomas develop as the result of multiple genetic and epigenetic changes in the precursor ovarian surface epithelial (OSE) cells which result in a malignant phenotype. We investigated changes in gene expression in ovarian adenocarcinoma using a cDNA array containing 588 known human genes. We found that intercellular adhesion molecule-1 (ICAM-1) was expressed at lower levels in the ovarian tumour cell lines OAW42, PEO1 and JAM than in the immortalised human ovarian surface epithelial cell line HOSE 17.1. Further investigation revealed ICAM-1 was expressed in the surface epithelium of normal ovaries and both mRNA and protein expression levels were reduced in the majority of ovarian adenocarcinoma cell lines and primary tumours. ICAM-1 expression was increased in 8/8 cell lines treated with the de novo methyltransferase inhibitor 5-aza-2′-deoxycytidine, indicating that methylation of CpG islands may play a role in the down-regulation of its expression in primary tumours. There was a significant association between patients whose tumours expressed ICAM-1 and survival (P= 0.03), suggesting that expression levels of ICAM-1 may have clinical relevance. © 2001 Cancer Research Campaign
Keywords: ovarian adenocarcinoma, ICAM-1, 5-aza-2′-deoxycytidine, loss of heterozygosity, cDNA array
Full Text
The Full Text of this article is available as a PDF (136.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amfo K., Neyns B., Teugels E., Lissens W., Bourgain C., De Sutter P., Vandamme B., Vamos E., De Grève J. Frequent deletion of chromosome 19 and a rare rearrangement of 19p13.3 involving the insulin receptor gene in human ovarian cancer. Oncogene. 1995 Jul 20;11(2):351–358. [PubMed] [Google Scholar]
- Buick R. N., Pullano R., Trent J. M. Comparative properties of five human ovarian adenocarcinoma cell lines. Cancer Res. 1985 Aug;45(8):3668–3676. [PubMed] [Google Scholar]
- Burno D. K., Fabian D. F., Lefor A. T. ICAM-1 increases in vitro adhesion and cytotoxicity in a murine fibrosarcoma. J Surg Res. 1996 Feb 1;60(2):398–402. doi: 10.1006/jsre.1996.0065. [DOI] [PubMed] [Google Scholar]
- Burno D. K., Kyprianou N., Sartor W. M., Fabian D. F., Turner J., Vu T., Patel A., Trimbach C., Lefor A. T. Transfection of a murine fibrosarcoma with intercellular adhesion molecule-1 enhances the response to adoptive immunotherapy. Surgery. 1995 Aug;118(2):237–244. doi: 10.1016/s0039-6060(05)80329-0. [DOI] [PubMed] [Google Scholar]
- Chenevix-Trench G., Leary J., Kerr J., Michel J., Kefford R., Hurst T., Parsons P. G., Friedlander M., Khoo S. K. Frequent loss of heterozygosity on chromosome 18 in ovarian adenocarcinoma which does not always include the DCC locus. Oncogene. 1992 Jun;7(6):1059–1065. [PubMed] [Google Scholar]
- Cheng P., Schmutte C., Cofer K. F., Felix J. C., Yu M. C., Dubeau L. Alterations in DNA methylation are early, but not initial, events in ovarian tumorigenesis. Br J Cancer. 1997;75(3):396–402. doi: 10.1038/bjc.1997.64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- D'Angelica M., Tung C., Allen P., Halterman M., Delman K., Delohery T., Klimstra D., Brownlee M., Federoff H., Fong Y. Herpes simplex virus (HSV)-mediated ICAM-1 gene transfer abrogates tumorigenicity and induces anti-tumor immunity. Mol Med. 1999 Sep;5(9):606–616. [PMC free article] [PubMed] [Google Scholar]
- Diamond M. S., Staunton D. E., Marlin S. D., Springer T. A. Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation. Cell. 1991 Jun 14;65(6):961–971. doi: 10.1016/0092-8674(91)90548-d. [DOI] [PubMed] [Google Scholar]
- Fearon E. R. BRCA1 and E-cadherin promoter hypermethylation and gene inactivation in cancer-association or mechanism? J Natl Cancer Inst. 2000 Apr 5;92(7):515–517. doi: 10.1093/jnci/92.7.515. [DOI] [PubMed] [Google Scholar]
- Hamilton T. C., Young R. C., McKoy W. M., Grotzinger K. R., Green J. A., Chu E. W., Whang-Peng J., Rogan A. M., Green W. R., Ozols R. F. Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res. 1983 Nov;43(11):5379–5389. [PubMed] [Google Scholar]
- Johnson J. P. Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. Cancer Metastasis Rev. 1991 May;10(1):11–22. doi: 10.1007/BF00046840. [DOI] [PubMed] [Google Scholar]
- Johnson J. P., Stade B. G., Holzmann B., Schwäble W., Riethmüller G. De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci U S A. 1989 Jan;86(2):641–644. doi: 10.1073/pnas.86.2.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaiserlian D., Rigal D., Abello J., Revillard J. P. Expression, function and regulation of the intercellular adhesion molecule-1 (ICAM-1) on human intestinal epithelial cell lines. Eur J Immunol. 1991 Oct;21(10):2415–2421. doi: 10.1002/eji.1830211018. [DOI] [PubMed] [Google Scholar]
- Kikuchi T., Joki T., Akasaki Y., Abe T., Ohno T. Induction of antitumor immunity using intercellular adhesion molecule 1 (ICAM-1) transfection in mouse glioma cells. Cancer Lett. 1999 Aug 3;142(2):201–206. doi: 10.1016/s0304-3835(99)00169-x. [DOI] [PubMed] [Google Scholar]
- Koyama S., Ebihara T., Fukao K. Expression of intercellular adhesion molecule 1 (ICAM-1) during the development of invasion and/or metastasis of gastric carcinoma. J Cancer Res Clin Oncol. 1992;118(8):609–614. doi: 10.1007/BF01211806. [DOI] [PubMed] [Google Scholar]
- Kruk P. A., Maines-Bandiera S. L., Auersperg N. A simplified method to culture human ovarian surface epithelium. Lab Invest. 1990 Jul;63(1):132–136. [PubMed] [Google Scholar]
- Langdon S. P., Lawrie S. S., Hay F. G., Hawkes M. M., McDonald A., Hayward I. P., Schol D. J., Hilgers J., Leonard R. C., Smyth J. F. Characterization and properties of nine human ovarian adenocarcinoma cell lines. Cancer Res. 1988 Nov 1;48(21):6166–6172. [PubMed] [Google Scholar]
- Lin H., Huber R., Schlessinger D., Morin P. J. Frequent silencing of the GPC3 gene in ovarian cancer cell lines. Cancer Res. 1999 Feb 15;59(4):807–810. [PubMed] [Google Scholar]
- McCluskey L. L., Chen C., Delgadillo E., Felix J. C., Muderspach L. I., Dubeau L. Differences in p16 gene methylation and expression in benign and malignant ovarian tumors. Gynecol Oncol. 1999 Jan;72(1):87–92. doi: 10.1006/gyno.1998.5235. [DOI] [PubMed] [Google Scholar]
- Natali P., Nicotra M. R., Cavaliere R., Bigotti A., Romano G., Temponi M., Ferrone S. Differential expression of intercellular adhesion molecule 1 in primary and metastatic melanoma lesions. Cancer Res. 1990 Feb 15;50(4):1271–1278. [PubMed] [Google Scholar]
- Ogawa Y., Hirakawa K., Nakata B., Fujihara T., Sawada T., Kato Y., Yoshikawa K., Sowa M. Expression of intercellular adhesion molecule-1 in invasive breast cancer reflects low growth potential, negative lymph node involvement, and good prognosis. Clin Cancer Res. 1998 Jan;4(1):31–36. [PubMed] [Google Scholar]
- Parkin D. M., Pisani P., Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer. 1999 Mar 15;80(6):827–841. doi: 10.1002/(sici)1097-0215(19990315)80:6<827::aid-ijc6>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
- Schwaeble W., Kerlin M., Meyer zum Büschenfelde K. H., Dippold W. De novo expression of intercellular adhesion molecule 1 (ICAM-1, CD54) in pancreas cancer. Int J Cancer. 1993 Jan 21;53(2):328–333. doi: 10.1002/ijc.2910530226. [DOI] [PubMed] [Google Scholar]
- Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
- Springer T. A., Dustin M. L., Kishimoto T. K., Marlin S. D. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol. 1987;5:223–252. doi: 10.1146/annurev.iy.05.040187.001255. [DOI] [PubMed] [Google Scholar]
- Strathdee G., MacKean M. J., Illand M., Brown R. A role for methylation of the hMLH1 promoter in loss of hMLH1 expression and drug resistance in ovarian cancer. Oncogene. 1999 Apr 8;18(14):2335–2341. doi: 10.1038/sj.onc.1202540. [DOI] [PubMed] [Google Scholar]
- Tomita Y., Nishiyama T., Watanabe H., Fujiwara M., Sato S. Expression of intercellular adhesion molecule-1 (ICAM-1) on renal-cell cancer: possible significance in host immune responses. Int J Cancer. 1990 Dec 15;46(6):1001–1006. doi: 10.1002/ijc.2910460609. [DOI] [PubMed] [Google Scholar]
- Tsao S. W., Mok S. C., Fey E. G., Fletcher J. A., Wan T. S., Chew E. C., Muto M. G., Knapp R. C., Berkowitz R. S. Characterization of human ovarian surface epithelial cells immortalized by human papilloma viral oncogenes (HPV-E6E7 ORFs). Exp Cell Res. 1995 Jun;218(2):499–507. doi: 10.1006/excr.1995.1184. [DOI] [PubMed] [Google Scholar]
- Uzendoski K., Kantor J. A., Abrams S. I., Schlom J., Hodge J. W. Construction and characterization of a recombinant vaccinia virus expressing murine intercellular adhesion molecule-1: induction and potentiation of antitumor responses. Hum Gene Ther. 1997 May 1;8(7):851–860. doi: 10.1089/hum.1997.8.7-851. [DOI] [PubMed] [Google Scholar]
- Vogetseder W., Feichtinger H., Schulz T. F., Schwaeble W., Tabaczewski P., Mitterer M., Böck G., Marth C., Dapunt O., Mikuz G. Expression of 7F7-antigen, a human adhesion molecule identical to intercellular adhesion molecule-1 (ICAM-1) in human carcinomas and their stromal fibroblasts. Int J Cancer. 1989 May 15;43(5):768–773. doi: 10.1002/ijc.2910430504. [DOI] [PubMed] [Google Scholar]
- Wang Z. J., Churchman M., Campbell I. G., Xu W. H., Yan Z. Y., McCluggage W. G., Foulkes W. D., Tomlinson I. P. Allele loss and mutation screen at the Peutz-Jeghers (LKB1) locus (19p13.3) in sporadic ovarian tumours. Br J Cancer. 1999 Apr;80(1-2):70–72. doi: 10.1038/sj.bjc.6690323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ward B. G., Wallace K., Shepherd J. H., Balkwill F. R. Intraperitoneal xenografts of human epithelial ovarian cancer in nude mice. Cancer Res. 1987 May 15;47(10):2662–2667. [PubMed] [Google Scholar]
- Wei K., Wilson J. G., Jurgensen C. H., Iannone M. A., Wolberg G., Huber B. E. Xenogeneic ICAM-1 gene transfer suppresses tumorigenicity and generates protective antitumor immunity. Gene Ther. 1996 Jun;3(6):531–541. [PubMed] [Google Scholar]
- Wilson A. P. Characterization of a cell line derived from the ascites of a patient with papillary serous cystadenocarcinoma of the ovary. J Natl Cancer Inst. 1984 Mar;72(3):513–521. [PubMed] [Google Scholar]
- Wolf C. R., Hayward I. P., Lawrie S. S., Buckton K., McIntyre M. A., Adams D. J., Lewis A. D., Scott A. R., Smyth J. F. Cellular heterogeneity and drug resistance in two ovarian adenocarcinoma cell lines derived from a single patient. Int J Cancer. 1987 Jun 15;39(6):695–702. doi: 10.1002/ijc.2910390607. [DOI] [PubMed] [Google Scholar]
- Wong A. S., Maines-Bandiera S. L., Rosen B., Wheelock M. J., Johnson K. R., Leung P. C., Roskelley C. D., Auersperg N. Constitutive and conditional cadherin expression in cultured human ovarian surface epithelium: influence of family history of ovarian cancer. Int J Cancer. 1999 Apr 12;81(2):180–188. doi: 10.1002/(sici)1097-0215(19990412)81:2<180::aid-ijc3>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
- Woods L. K., Morgan R. T., Quinn L. A., Moore G. E., Semple T. U., Stedman K. E. Comparison of four new cell lines from patients with adenocarcinoma of the ovary. Cancer Res. 1979 Nov;39(11):4449–4459. [PubMed] [Google Scholar]