Polyploidisation of metastatic colon carcinoma cells by microtubule and tubulin interacting drugs: effect on proteolytic activity and invasiveness.
When SW620 colon cancer-derived metastatic cells were exposed to nanomolar concentrations of Taxol, colchicine or (Z)-3,5,4'-trimethoxystilbene (R3), huge aneuploid, polynuclear cells survived the treatment. These cells released considerable amounts of the matrix metalloproteinase matrilysin (MMP-7), and tissue-type plasminogen activator (tPA) into the surrounding culture medium. MMP-7, and other proteolytic enzymes were highly expressed by these cells. In spite of their enormous size, the polyploid cells exhibited a considerable migratory capacity, as was demonstrated by their migration through an artificial basement membrane. While colchicine and R3-treated cells showed an inverse relationship between drug concentration and invasiveness, treatment with Taxol increased the capacity of the SW620 cells to penetrate through the membrane. The invasive capacity was not correlated with the induction and release of proteolytic enzymes. The idea that expression and release of proteolytic enzymes is a fundamental prerequisite of tumour cell invasiveness is generally accepted. The ability of the cells to respond to chemotactic signalling, and the filamentous structures of the cells, together with several cell adhesion factors, which are the basis of cell migration, are prerequisites of invasiveness. These factors are presumably different in the aneuploid cells produced by Taxol, colchicine and R3, and await scrutiny.
Seiler
Nikolaus
N
Laboratory of Nutritional Oncology, INSERM U392, IRCAD, BP 426 67091 Strabourg Cedex, France. nikolaus.seiler@ircad.u-strasbg.fr
Schneider
Yann
Y
Gossé
Francine
F
Schleiffer
René
R
Raul
Francis
F
D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003078:Colchicine / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects*; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology*; D011123:Polyploidy; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014404:Tubulin / Q000187:drug effects*
D014404:Tubulin; D010959:Tissue Plasminogen Activator; D020783:Matrix Metalloproteinase 7; D017239:Paclitaxel; D003078:Colchicine