Expression of FAP-1 by human colon adenocarcinoma: Implication for resistance against Fas-mediated apoptosis in cancer

H. Yao, E. Song, J. Chen, P. Hamar

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Although colon carcinoma cells express Fas receptors, they are resistant to Fas-mediated apoptosis. Defects within the intracellular Fas signal transduction may be responsible. We investigated whether the Fas-associated phosphatase-1 (FAP-1), an inhibitor of Fas signal transduction, contributed to this resistance in colon carcinomas. In vivo, apoptosis of cancer cells was detected in situ using terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL). FAP-1, FasR, and Fas ligand (FasL) were detected using immunohistochemistry. In vitro, colon carcinoma cells were primarily cultured, and their sensitivity to Fas-mediated apoptosis was evaluated by treatment with agonistic anti-FasR CH11 IgM monoclonal antibody in the presence or absence of synthetic Ac-SLV (serine-leucine-valine) tripeptide. Fas-associated phosphatase-1 expression was detected in 20 out of 28 colon adenocarcinomas. In vivo, a positive correlation between the percentage of apoptotic tumour cells and the number of FasL-positive tumour infiltrating lymphocytes was observed in FAP-1 negative cancers, but not in FAP-1-positive ones. Primarily cultured colon cancer cells, which were refractory to CH-11-induced apoptosis, had higher expression of FAP-1 on protein and mRNA levels than the sensitive group. Resistance to Fas-mediated apoptosis in tumour cells could be abolished by Ac-SLV tripetides. Fas-associated phosphatase-1 expression protects colon cancer cells from Fas-mediated apoptosis, and blockade of FAP-1 and FasR interaction sensitises tumour cells to Fas-dependent apoptosis.

Original languageEnglish
Pages (from-to)1718-1725
Number of pages8
JournalBritish Journal of Cancer
Volume91
Issue number9
DOIs
Publication statusPublished - Nov 1 2004

Fingerprint

Phosphoric Monoester Hydrolases
Colon
Adenocarcinoma
Apoptosis
Neoplasms
Fas Ligand Protein
Carcinoma
Colonic Neoplasms
Signal Transduction
CD95 Antigens
Tumor-Infiltrating Lymphocytes
Protein Phosphatase 1
DNA Nucleotidylexotransferase
In Situ Nick-End Labeling
Valine
human PTPN13 protein
Leucine
Serine
Immunoglobulin M
Cell Count

Keywords

  • Apoptosis
  • Colon neoplasms
  • Fas receptor
  • Fas-associated phosphatase-1
  • Immune escape

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression of FAP-1 by human colon adenocarcinoma : Implication for resistance against Fas-mediated apoptosis in cancer. / Yao, H.; Song, E.; Chen, J.; Hamar, P.

In: British Journal of Cancer, Vol. 91, No. 9, 01.11.2004, p. 1718-1725.

Research output: Contribution to journalArticle

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