Regulatory effect of interleukin-4 and interleukin-13 on colon cancer cell adhesion.
To assess the role of interleukin-4 (IL-4) and interleukin-13 (IL-13) in colon cancer cell-cell adhesion, we investigated the effect of both cytokines in human colon cancer cell line, colo205 cell-cell adhesion. IL-4 receptor was expressed on the cell surface of colo205, and recombinant IL-4 inhibited colo205 cell-cell adhesion in a dose-dependent fashion without inhibiting cell proliferation. Flow cytometric analysis revealed that monoclonal antibodies (mAbs) directed against E-cadherin and carcinoembryonic antigen (CEA) inhibited colo205 cell-cell adhesion and IL-4 significantly inhibited the expression of E-cadherin and CEA. IL-13 also inhibited colo205 cell-cell adhesion. These results indicated that IL-4 and IL-13 inhibited colon cancer cell-cell adhesion by down-regulation of E-cadherin and CEA molecules. We then investigated the expression of both cytokines from freshly isolated colon cancer tumour-infiltrating lymphocytes (TILs). With reverse transcription-polymerase chain reaction and flow cytometric analysis, we demonstrated that colon TILs expressed IL-4 and IL-13 mRNA and protein. These results suggest that Th 2 type cytokines IL-4 and IL-13 locally-produced from TILs may regulate colon cancer adhesion by down-regulation of adhesion molecules.
Kanai
T
T
Keio Cancer Center, Tokyo, Japan.
Watanabe
M
M
Hayashi
A
A
Nakazawa
A
A
Yajima
T
T
Okazawa
A
A
Yamazaki
M
M
Ishii
H
H
Hibi
T
T
D015820:Cadherins / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015820:Cadherins; D002272:Carcinoembryonic Antigen; D018793:Interleukin-13; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D015847:Interleukin-4