Using quantitative real-time polymerase chain reaction and Western blot, we found that overexpression of CD147 in MCF7 cells up-regulated MDR1, MMP2, and MMP9 on both transcription and expression levels, which promoted tumor cells metastasis and conferred them multidrug resistance to P-gp substrate drugs, as determined by in vitro invasion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
However, MDR1 RNA expression was less frequent in locally advanced tumors and was absent in the primary tumors of all six patients who had distant metastases.
The percentage of P-gp-expressing cells and the expression rate of P-gp gene both exhibited statistical differences between metastasis and no-metastasis groups (both P<0.05).
Apart from accelerating metastasis and inducing epithelial-mesenchymal transition, SATB1 was demonstrated to confer resistance to both P-glycoprotein-related and P-glycoprotein-non-related drugs on MCF7 cells, which was accompanied by decreasing accumulation of adriamycin in SATB1-overexpressing transfectants.
This study offers compelling evidence that (a) IGR-N-91 is a human neuroblastoma xenograft model able to induce metastasis in nude mice, (b) an increase in MYCN and MDR1 transcripts levels is associated with the metastatic process, and (c) IGR-N-91 provides a biological tool for the study of gene activations during tumor dissemination in neuroblastoma.
The finding that metastatic cells are capable of expressing MDR1, in contrast to the NB cells of the primary tumor, would certainly be an interesting topic for further study as work directed at understanding the progression to metastasis continues.
Examining ways of controlling human lung cancer metastases, we investigated the antimetastatic effect of chimeric monoclonal antibodies (MAbs) against P-glycoprotein and ganglioside GM2 (MH162 and KM966, respectively).
No significant relationship was found between the expression of the resistance-related proteins P-glycoprotein or glutathione S-transferase-pi and the incidence of metastases.
A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: continuous infusion doxorubicin, vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist.