A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin

Abstract

Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasion through matrigel and membrane pores, by decreased adhesion to extracellular matrix proteins and by increased motility. This may represent an in vitro model of a step in the metastatic process occurring subsequent to invasion. The paclitaxel-resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol-10p4p were resistant to paclitaxel, vincristine and docetaxel, but not to doxorubicin, carboplatin, etoposide or 5-fluorouracil. The doxorubidn-selected variants MDA-MB-435S-F/Adr-10p and MDA-MB-435S-F/Adr- 10p10p, in contrast, exhibited only small increases in resistance to doxorubicin, although they were slightly resistant to VP-16 and docetaxel, and exhibited increased sensitivity to paclitaxel, carboplatin and 5-fluorouracil. © 2004 Cancer Research UK.