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. 1999 Mar;79(7-8):1262–1269. doi: 10.1038/sj.bjc.6690202

FasL is more frequently expressed in liver metastases of colorectal cancer than in matched primary carcinomas

B Mann 1, A Gratchev 2, C Böhm 2, G Demel 3, B Trojanek 4, I Schmidt-Wolf 4, H Stein 3, C Hanski 2
PMCID: PMC2362258  PMID: 10098769

Abstract

Colorectal carcinoma cells have recently been shown to express Fas ligand (FasL). This ligand could allow the tumour cells to evade activated tumour-infiltrating lymphocytes (TILs) by inducing their apoptosis and would thus promote tumour survival and possibly metastasis formation. To test this hypothesis in vivo we analysed the expression of FasL mRNA and protein in paired tissue samples of normal colonic mucosa (N), primary colorectal carcinomas (T) and their metastases (M) from a total of 21 patients by four different methods. Additionally, the presence and activation status of infiltrating lymphocytes, which might contribute to the total amount of FasL in the tissue, was determined by semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) in the same samples. The frequency of FasL detection was 30–40% in T and was 60–100% in M, depending on the sensitivity of the method. Simultaneously, the amount of CD25 mRNA, used as a measure of the number of activated TILs, was in 90% of patients lower in M than in T. The increased frequency of FasL detection in liver metastases was therefore not due to the presence of activated TILs. We conclude that metastasizing subpopulations of colorectal tumour cells express FasL more frequently than the primary carcinomas and may be able to eliminate activated TILs in vivo via Fas/FasL-induced apoptosis or other hitherto unknown mechanisms. © 1999 Cancer Research Campaign

Keywords: colorectal carcinoma, progression, metastases, FasL, TILs, immune escape

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Selected References

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  1. Ambe K., Mori M., Enjoji M. S-100 protein-positive dendritic cells in colorectal adenocarcinomas. Distribution and relation to the clinical prognosis. Cancer. 1989 Feb 1;63(3):496–503. doi: 10.1002/1097-0142(19890201)63:3<496::aid-cncr2820630318>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  2. Barth R. J., Jr, Camp B. J., Martuscello T. A., Dain B. J., Memoli V. A. The cytokine microenvironment of human colon carcinoma. Lymphocyte expression of tumor necrosis factor-alpha and interleukin-4 predicts improved survival. Cancer. 1996 Sep 15;78(6):1168–1178. doi: 10.1002/(SICI)1097-0142(19960915)78:6<1168::AID-CNCR2>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  3. Bellgrau D., Gold D., Selawry H., Moore J., Franzusoff A., Duke R. C. A role for CD95 ligand in preventing graft rejection. Nature. 1995 Oct 19;377(6550):630–632. doi: 10.1038/377630a0. [DOI] [PubMed] [Google Scholar]
  4. Brunner T., Mogil R. J., LaFace D., Yoo N. J., Mahboubi A., Echeverri F., Martin S. J., Force W. R., Lynch D. H., Ware C. F. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature. 1995 Feb 2;373(6513):441–444. doi: 10.1038/373441a0. [DOI] [PubMed] [Google Scholar]
  5. De Maria R., Boirivant M., Cifone M. G., Roncaioli P., Hahne M., Tschopp J., Pallone F., Santoni A., Testi R. Functional expression of Fas and Fas ligand on human gut lamina propria T lymphocytes. A potential role for the acidic sphingomyelinase pathway in normal immunoregulation. J Clin Invest. 1996 Jan 15;97(2):316–322. doi: 10.1172/JCI118418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dhein J., Walczak H., Bäumler C., Debatin K. M., Krammer P. H. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) Nature. 1995 Feb 2;373(6513):438–441. doi: 10.1038/373438a0. [DOI] [PubMed] [Google Scholar]
  7. Ehl S., Hoffmann-Rohrer U., Nagata S., Hengartner H., Zinkernagel R. Different susceptibility of cytotoxic T cells to CD95 (Fas/Apo-1) ligand-mediated cell death after activation in vitro versus in vivo. J Immunol. 1996 Apr 1;156(7):2357–2360. [PubMed] [Google Scholar]
  8. French L. E., Hahne M., Viard I., Radlgruber G., Zanone R., Becker K., Müller C., Tschopp J. Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover. J Cell Biol. 1996 Apr;133(2):335–343. doi: 10.1083/jcb.133.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. French L. E., Tschopp J. Constitutive Fas ligand expression in several non-lymphoid mouse tissues: implications for immune-protection and cell turnover. Behring Inst Mitt. 1996 Oct;(97):156–160. [PubMed] [Google Scholar]
  10. Galle P. R., Hofmann W. J., Walczak H., Schaller H., Otto G., Stremmel W., Krammer P. H., Runkel L. Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. J Exp Med. 1995 Nov 1;182(5):1223–1230. doi: 10.1084/jem.182.5.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Griffith T. S., Brunner T., Fletcher S. M., Green D. R., Ferguson T. A. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995 Nov 17;270(5239):1189–1192. doi: 10.1126/science.270.5239.1189. [DOI] [PubMed] [Google Scholar]
  12. Hahne M., Rimoldi D., Schröter M., Romero P., Schreier M., French L. E., Schneider P., Bornand T., Fontana A., Lienard D. Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science. 1996 Nov 22;274(5291):1363–1366. doi: 10.1126/science.274.5291.1363. [DOI] [PubMed] [Google Scholar]
  13. Kang S. M., Schneider D. B., Lin Z., Hanahan D., Dichek D. A., Stock P. G., Baekkeskov S. Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat Med. 1997 Jul;3(7):738–743. doi: 10.1038/nm0797-738. [DOI] [PubMed] [Google Scholar]
  14. Kemmner W., Schlag P., Brossmer R. A rapid and simple procedure for dissociation of tumor tissue from the human colon. J Cancer Res Clin Oncol. 1987;113(4):400–401. doi: 10.1007/BF00397727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mulder W. M., Bloemena E., Stukart M. J., Kummer J. A., Wagstaff J., Scheper R. J. T cell receptor-zeta and granzyme B expression in mononuclear cell infiltrates in normal colon mucosa and colon carcinoma. Gut. 1997 Jan;40(1):113–119. doi: 10.1136/gut.40.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Möller P., Koretz K., Leithäuser F., Brüderlein S., Henne C., Quentmeier A., Krammer P. H. Expression of APO-1 (CD95), a member of the NGF/TNF receptor superfamily, in normal and neoplastic colon epithelium. Int J Cancer. 1994 May 1;57(3):371–377. doi: 10.1002/ijc.2910570314. [DOI] [PubMed] [Google Scholar]
  17. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  18. Niehans G. A., Brunner T., Frizelle S. P., Liston J. C., Salerno C. T., Knapp D. J., Green D. R., Kratzke R. A. Human lung carcinomas express Fas ligand. Cancer Res. 1997 Mar 15;57(6):1007–1012. [PubMed] [Google Scholar]
  19. O'Connell J., O'Sullivan G. C., Collins J. K., Shanahan F. The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand. J Exp Med. 1996 Sep 1;184(3):1075–1082. doi: 10.1084/jem.184.3.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Oshimi Y., Oda S., Honda Y., Nagata S., Miyazaki S. Involvement of Fas ligand and Fas-mediated pathway in the cytotoxicity of human natural killer cells. J Immunol. 1996 Oct 1;157(7):2909–2915. [PubMed] [Google Scholar]
  21. Seino K., Kayagaki N., Okumura K., Yagita H. Antitumor effect of locally produced CD95 ligand. Nat Med. 1997 Feb;3(2):165–170. doi: 10.1038/nm0297-165. [DOI] [PubMed] [Google Scholar]
  22. Shimizu Y., Watanabe A., Whiteside T. L. Memory T-lymphocytes are the main population of tumor-infiltrating lymphocytes obtained from human primary liver tumors. J Hepatol. 1992 Sep;16(1-2):197–202. doi: 10.1016/s0168-8278(05)80115-1. [DOI] [PubMed] [Google Scholar]
  23. Shiraki K., Tsuji N., Shioda T., Isselbacher K. J., Takahashi H. Expression of Fas ligand in liver metastases of human colonic adenocarcinomas. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6420–6425. doi: 10.1073/pnas.94.12.6420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Strand S., Hofmann W. J., Hug H., Müller M., Otto G., Strand D., Mariani S. M., Stremmel W., Krammer P. H., Galle P. R. Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion? Nat Med. 1996 Dec;2(12):1361–1366. doi: 10.1038/nm1296-1361. [DOI] [PubMed] [Google Scholar]
  25. Suda T., Takahashi T., Golstein P., Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993 Dec 17;75(6):1169–1178. doi: 10.1016/0092-8674(93)90326-l. [DOI] [PubMed] [Google Scholar]
  26. Walker P. R., Saas P., Dietrich P. Y. Role of Fas ligand (CD95L) in immune escape: the tumor cell strikes back. J Immunol. 1997 May 15;158(10):4521–4524. [PubMed] [Google Scholar]
  27. Zeytun A., Hassuneh M., Nagarkatti M., Nagarkatti P. S. Fas-Fas ligand-based interactions between tumor cells and tumor-specific cytotoxic T lymphocytes: a lethal two-way street. Blood. 1997 Sep 1;90(5):1952–1959. [PubMed] [Google Scholar]

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