Drug resistant tumor cells have increased levels of tumor markers for invasion and metastasis

The association between drug-resistance and three markers for invasive capa city: cathepsin D (Cath D) urokinase type plasminogen activator (uPA) and i nhibitor of plasminogen activator type I (PAI-I) was examined in nine cervi cal and laryngeal carcinoma cell lines resistant to different cylostatics. The level of Cath D was measured by solid phase two-site immunoradiometric assay, while uPA and PAI-1 concentrations were determined by use of LISA. A ll drug resistant cell lines had increased concentration of cathepsin D. uP A levels were similar in par-ental and drug resistant cervical carcinoma ce lls, but significantly higher in all examined drug resistant laryngeal carc inoma cells. In cervical carcinoma cells, PAI-I concentrations were similar in parental and cisplatin resistant, but significantly higher in doxorubic in resistant cells. In laryngeal cat-cinema cells, no increase in concentra tions of PAI-I was determined in the three from five resistant cell lines. There was no uPA in conditioned medium of parental or drug resistant cells. PAI-I was detected in conditioned medium. Its levels were significantly in n eased in the medium of two cervical and three laryngeal drug resistant ca rcinoma cells. Thus, our results suggest that drug-resistance may be accomp anied by increased levels of tumor associated proteases and/or its inhibito r.