Repopulation of osteosarcoma cells after treatment with doxorubicin in the presence of extracellular matrix biopolymers.
OBJECTIVE
To elucidate the role of extracellular matrix (ECM) in repopulation capacity of osteosarcoma cells after doxorubicin treatment.


METHODS
OSCORT cells established in our laboratory from a human osteosarcoma, were treated with doxorubicin in monolayer for 4 h, then cells were further incubated either in monolayer or in ECM-containing three-dimensional cell-culture (3-DCC), apoptosis induction and changes in cell number were measured. Alkaline comet assay was applied to estimate DNA damage, immunoblot technique and immunocytochemistry were used to investigate p53 protein synthesis, and the repopulating capacity in monolayer culture and in ECM-based 3-DCC, after doxorubicin treatment was measured. In addition to OSCORT culture five other human cell lines (HT-1080, PC-3, MDA-MB231, A-431 and ZR-75-1) were used to compare the antimigratory and antiproliferative effects of doxorubicin.


RESULTS
The apoptotic index, the extent of DNA damage and the representation of p53 were much lower in the OSCORT cell cultures if the cells were exposed to ECM after treatment with doxorubicin. The doxorubicin-treated OSCORT cells transferred from the monolayer culture were not able to proliferate at all, at the same time, the cytoprotection provided by ECM prevailed upon transferring the cells into plastic dish, and resulted in potent repopulation capacity of the cells.


CONCLUSIONS
Present data indicate that ECM contributes to failure in therapy of human osteosarcoma in clinical situation. Overall, the application of ECM-based 3-DCC could be suggested as an appropriate model system for the better understanding of antitumor drug action and hereby to set the stage for promising novel pharmacological approaches in cancer therapy.
1st Institute of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Budapest, Hungary.
Revekka
R
Harisi
József
J
Dudás
Gábor
G
Pogány
Ferenc
F
Timár
Júlia Nagy
JN
Oláh
Miklós
M
Szendroi
András
A
Jeney
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001704:Biopolymers / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D012516:Osteosarcoma / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000903:Antibiotics, Antineoplastic; D001704:Biopolymers; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin