We have previously shown that the selection of cancer cell lines with chemotherapeutic agents can alter the invasive potential of the cells, resulting in a superinvasive phenotype, where cells not only invade through matrigel and migrate through membrane pores, but also subsequently detach from the underside of the invasion chamber, survive in suspension and ultimately attach to and grow on the bottom of the well beneath the insert. In order to determine the significance of this in vivo, the following experiments were performed. 4T1-GFP mouse mammary adenocarcinoma cells were pulse-selected with doxorubicin or paclitaxel. Three variants with differing invasiveness were isolated and their metastatic potential in vivo was compared to the parental cell line, through injection into the mammary fat pad of BALB/c mice and subsequent primary tumour growth and metastasis to the lungs measurement. Increasing superinvasiveness was inversely linked to tumour diameter (p < 0.005). The superinvasive status predicted the incidence of lung nodules in 2/3 variant groups, with significant differences in the number of nodules (p < 0.001). The in vitro superinvasive phenotype coupled with decreased adhesion may predict for metastatic potential in vivo.
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