help button home button Am J Pathol International Conference on Pathology of Chest Diseases
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yoong, K. F.
Right arrow Articles by Adams, D. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yoong, K. F.
Right arrow Articles by Adams, D. H.
(American Journal of Pathology. 1999;154:693-703.)
© 1999 American Society for Investigative Pathology

Regular Articles

Fas/Fas Ligand Interaction in Human Colorectal Hepatic Metastases

A Mechanism of Hepatocyte Destruction to Facilitate Local Tumor Invasion

Khong F. Yoong, Simon C. Afford, Satinder Randhawa, Stefan G. Hubscher and David H. Adams

From the MRC Centre for Immune Regulation at University of Birmingham Liver Research Labóratories, Queen Elizabeth Hospital, Birmingham, United Kingdom

This study demonstrates a novel role for the Fas pathway in the promotion of local tumor growth by inducing apoptotic cell death in normal hepatocytes at the tumor margin in colorectal hepatic metastases. Our results show that >85% of lymphocytes infiltrating colorectal liver cancer express high levels of Fas-ligand (Fas-L) by flow cytometry. Using immunohistochemistry of tumor tissue we showed strong Fas expression in noninvolved hepatocytes, whereas Fas-L expression was restricted to tumor cells and infiltrating lymphocytes at the tumor margin. Apoptosis was observed in 45 ± 13% of the Fashigh hepatocytes at the tumor margin whereas only 7 ± 3% tumor cells were apoptotic (n = 10). In vitro, primary human hepatocytes expressed Fas receptor and crosslinking with anti-Fas antibody induced apoptosis in 44 ± 5% of the cells compared with 4.6 ± 1.0% in untreated controls (P = 0.004). Both tumor-infiltrating lymphocytes (TIL) and human metastatic colon cancer cells cells are able to induce Fas-mediated apoptosis of primary human hepatocytes in coculture cytotoxic assays. TIL induced apoptosis in 47 ± 9% hepatocytes compared with control 4.3 ± 1.0% (P = 0.009) and this effect was reduced by anti-human Fas-L mAb (18.7 ± 1.3%, P = 0.009). SW620 cells induced apoptosis in 26 ± 2% hepatocytes compared with control 5.6 ± 1.7% (P = 0.004) and this was reduced to 11.2 ± 1.8% (P = 0.004) in the presence of anti-human Fas-L mAb. These data suggest that the inflammatory response at the margin of colorectal liver metastases induces Fas expression in surrounding hepatocytes, allowing them to be killed by Fas-L-bearing TIL or tumor cells and facilitating the invasion of the tumor into surrounding liver tissue.




This article has been cited by other articles:


Home page
 Int ImmunolHome page
M. S. Renna, S. G. Correa, C. Porporatto, C. M. Figueredo, M. P. Aoki, M. G. Paraje, and C. E. Sotomayor
Hepatocellular apoptosis during Candida albicans colonization: involvement of TNF-{alpha} and infiltrating Fas-L positive lymphocytes
Int. Immunol., December 1, 2006; 18(12): 1719 - 1728.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
G. A. Parker and C. A. Picut
Liver Immunobiology
Toxicol Pathol, January 1, 2005; 33(1): 52 - 62.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
G.-i. Kusakai, A. Suzuki, T. Ogura, S.'i. Miyamoto, A. Ochiai, M. Kaminishi, and H. Esumi
ARK5 Expression in Colorectal Cancer and Its Implications for Tumor Progression
Am. J. Pathol., March 1, 2004; 164(3): 987 - 995.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y.-G. Yoo, S. H. Oh, E. S. Park, H. Cho, N. Lee, H. Park, D. K. Kim, D.-Y. Yu, J. K. Seong, and M.-O. Lee
Hepatitis B Virus X Protein Enhances Transcriptional Activity of Hypoxia-inducible Factor-1{alpha} through Activation of Mitogen-activated Protein Kinase Pathway
J. Biol. Chem., October 3, 2003; 278(40): 39076 - 39084.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J.-J. Liu, A. Nilsson, S. Oredsson, V. Badmaev, W.-Z. Zhao, and R.-D. Duan
Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells
Carcinogenesis, December 1, 2002; 23(12): 2087 - 2093.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
K. A. Whartenby, E. E. Straley, H. Kim, F. Racke, V. Tanavde, K. S. Gorski, L. Cheng, D. M. Pardoll, and C. I. Civin
Transduction of donor hematopoietic stem-progenitor cells with Fas ligand enhanced short-term engraftment in a murine model of allogeneic bone marrow transplantation
Blood, October 16, 2002; 100(9): 3147 - 3154.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
H H J Backus, C J Van Groeningen, W Vos, D F Dukers, E Bloemena, D Wouters, H M Pinedo, and G J Peters
Differential expression of cell cycle and apoptosis related proteins in colorectal mucosa, primary colon tumours, and liver metastases
J. Clin. Pathol., March 1, 2002; 55(3): 206 - 211.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
I TINHOFER, H WYKYPIEL, I MARSCHITZ, T HENN, R GREIL;, M W BENNETT, J O'CONNELL, D ROCHE, C BRADY, J KELLY, et al.
Gastric cancer cell lines lack Fas ligand (FasL) expression but kill T cells via a FasL independent pathway • Reply
Gut, May 1, 2000; 46(5): 738 - 740.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. J. Pinkoski, T. Brunner, D. R. Green, and T. Lin
Fas and Fas ligand in gut and liver
Am J Physiol Gastrointest Liver Physiol, March 1, 2000; 278(3): G354 - G366.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the American Society for Investigative Pathology.