[Functional significance of CD40 and CD40 ligand linking on human lung cells].
OBJECTIVE
To determine the possible functional significance of CD40 and CD40 ligand (CD154) linking on human lung carcinomas and to assess the potential of CD40 as a therapeutic target.


METHODS
We evaluated the effect of CD40L on the surface expression of major histocompatibility complex class I (MHC-I), Fas, bcl2, CD54, epidermal growth factor receptor (EGFR), p-glucoprotein (PGP), lung related protein (LRP), cell cycle, cell apoptosis and growth kinetics of 7 lung cancer cell lines (including 1 CD40-transfected cell line GLC-82/CD40) by gene cloning, Western blotting, and flow cytometry etc.


RESULTS
Significant increased expression of MHC-I, CD54 and Fas was observed in 4 tumor lines expressing high levels of CD40 after CD40L (0.1 micro g/ml) linked to CD40. CD40L (0.1 micro g/ml or greater) in the fifth day was found to significantly inhibit the proliferation of 4 cell lines expressing high levels of CD40, decreased the percentage of aneuploid cell, and inhibited S-phase cells entering G2/M phase. The effect of CD40 cross-linking was reversible. CD40-moderate and low and negative tumor did not respond to CD40L. All of 7 cell lines show no significant changes in apoptosis in either the experimental (CD40L pulsed) or control (medium only) cell cultures.


CONCLUSIONS
Expression of CD40 on lung tumors cells expressing high level of CD40 (including CD40-transfected cells) may represent a potential therapeutic target.
Cui
Wei
W
Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Li
Long-yun
LY
D019013:CD40 Antigens / Q000032:analysis / Q000502:physiology*; D023201:CD40 Ligand / Q000494:pharmacology* / Q000627:therapeutic use; D066246:ErbB Receptors / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
D019013:CD40 Antigens; D015395:Histocompatibility Antigens Class I; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D023201:CD40 Ligand; D066246:ErbB Receptors