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.
Subject(s)
Colorectal Neoplasms/metabolism , Liver Neoplasms/metabolism , Membrane Glycoproteins/metabolism , Neoplasm Proteins/metabolism , Colorectal Neoplasms/pathology , Fas Ligand Protein , Humans , Immunoblotting , In Situ Hybridization , Liver/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Lymphocyte Activation , Lymphocytes, Tumor-Infiltrating , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, CulturedABSTRACT
The protein beta-catenin can not be degraded in CRC due to different reasons. This leads to an increased formation of beta-catenin/Tcf4 complex, which has a strong transcription factor activity. We investigated the mRNA expression of beta-catenin and Tcf4 in N, T and M in 12 cell lines and in tissues samples of 14 patients. We found a significant increase of beta-catenin mRNA expression in the primary tumors and in the metastases. These data show for the first time that apart from the known mechanisms the overexpression of beta-catenin mRNA can be an additional factor contributing to the increase of beta-catenin amount in cells of CRC. The resulting increased transcription of hitherto unknown target genes might be involved in the progression and the metastatic process of CRC.
