Modulation of the CXC-chemokine expression profile on tumor cells by the immunosuppressive drug mycophenolate mofetil.
The most undesirable complication of an effective immunosuppressive therapy is neoplastic tumor recurrence or the development of de novo cancer. Though the immunosuppressive drug, mycophenolate mofetil (MMF), has been introduced into clinical practice, no data dealing with the influence of MMF on tumor cell malignancy are available. We analyzed the adhesion capacity of colon, pancreas and kidney carcinoma cell lines to endothelium, as well as their chemokine profile before and after MMF treatment. Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1, 1, and 10 microM MMF and compared to unstimulated controls. Chemokine analysis concentrated on the CXC family, including 6 CXC-receptors (CXCR) and 15 CXC-ligands (CXCL), and was carried out by reverse transcriptase-polymerase chain reaction and flow cytometry. MMF strongly diminished the adhesion capacity of HT-29 colon tumor cells but not of DanG pancreas tumor cells to endothelium. MMF also had a strong impact on the chemokine profile of colon, kidney and pancreas carcinomas, whereby individual changes were observed, depending on the tumor type. Down-regulating effects on chemokines did not correlate with down-regulating effects on tumor cell adhesion. Since several of the chemokines investigated are regulatory elements in the process of cell transformation, dissemination and angiogenesis, we speculate that MMF might prevent post-transplant tumor recurrence and transendothelial migration. However, the efficacy of MMF might differ according to the tumor type.
Engl
Tobias
T
Zentrum der Chirurgie, Klinik für Urologie und Kinderurologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Relja
Borna
B
Natsheh
Iyad
I
Makarevic
Jasmina
J
Müller
Iris
I
Beecken
Wolf-Dietrich
WD
Jonas
Dietger
D
Blaheta
Roman A
RA
D002448:Cell Adhesion / Q000187:drug effects; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics*; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured
D019743:Chemokines, CXC; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D009173:Mycophenolic Acid