Congruence of SQM1 protein expression with methotrexate sensitivity and transport

Expression of SQM1 protein, a membrane protein, was shown to be reduced in human squamous carcinoma of the head and neck (SqCHN) cell lines made less sensitive to methotrexate (MTX). High correlation of SQM1 protein expression with MTX transport (r = .94) and MTX sensitivity (r = .94) was found in MTX-resistant sublines developed from a clonally drived SqCHN cell line, SCC 15S1. Unlike SQM1 protein, there was no significant difference in amount or molecular weight of reduced-folate binding protein found in the membrane of a MTX-resistant subline, SCC15R1-3 and SCC15S1. Furthermore, MTX surface membrane binding was not significantly altered in SCC15R1-3. Compared to SCC15S1 parent cell line, SCC15R1-3 subline with similar DHFR enzyme level and MTX polyglutamylation showed a marked reduction in MTX uptake due to a decrease in Vmax without a significant change in Kt. These findings suggest the existence of membrane molecules like SQM1 protein that may indirectly affect MTX transport.