METASTATIC ACTIVITY OF THE MCF-7 MULTIDRUG-RESISTANT CELL-LINE CULTURED IN SPHEROIDS

The occurrence of solid tumors spreading through the body is a major c oncern for the clinicians. Moreover in numerous cases, metastases exhi bit a multidrug resistant (MDR) pattern. This dual characteristic stil l remains supported by few biological explanations. The purpose of our study was to compare invasive properties of sensitive and MDR MCF-7 c ells. Spheroids were chosen as experimental model since they exhibit a number of characteristics (i.e. tridimensional structure) close to th e growth of an in vivo tumor. MDR spheroids formed more compact struct ures compared to sensitive ones. In every experiment, spheroids made f rom sensitive cells were more resistant to doxorubicin than the same c ells grown as monolayers, a characteristic not observed with MDR cells . On an other hand, a form of multicellular resistance appeared in sph eroids of sensitive cells, a fact which was not present in MDR spheroi ds. Incubation of MDR spheroids in Boyden's chambers put in evidence i ncreased motility and invasive properties through Matrigel which were not present in sensitive MCF-7 cells. Zymograms of culture media and m embrane extracts were performed in polyacrylamide gels. Two metallopro teases, progelatinases A et B were detected in culture media condition ed by monolayers and spheroids of both sensitive and resistant cells. In contrast, 2 unidentified serine pretenses were detected only in med ia conditioned by spheroids of both cell types. An intense band of pro -MMP2 was present only in membrane extracts from MDR spheroids. Taken all together, these results demonstrate that spheroids of MDR cells ex hibit a number of properties which could lead to an increased ability to form metastases.