title: Antiproliferative and antimigratory effects of doxorubicin in human osteosarcoma cells exposed to extracellular matrix.
abstract: Osteosarcoma cells are involved in the remodeling of the extracellular matrix (ECM) that affects their growth, invasive and metastatic activities. The tumour ECM provided effective protection against chemotherapy agents in several previously studied malignancies. The current study examined the effects of doxorubicin on cells that were migrated into a 3-dimensional extracellular matrix gel (ECM-gel) in comparison with its effects on cells remaining in the monolayer compartment. A human osteosarcoma cell line (OSCORT) was treated with doxorubicin in monolayer culture for 4 or 24 hours, and then overlaid by ECM-gel for 24 hours. Tumour cells remaining in the monolayer were separated from the cells migrated into ECM-gel, and both of them were characterized. OSCORT cells migrated into ECM-gel showed elevated levels and activity of topoisomerase II, increased protein expression of beta1 integrin and matrix metalloproteinase-9 activity. Doxorubicin treatment for 4 hours resulted in increased cytotoxicity in the monolayer compartment relative to the cells migrated into ECM-gel, whereas 24-hour treatment at a low concentration (0.01 microg/ml) showed an antimigratory effect. Different antiproliferative and antimigratory effects of doxorubicin treatment schedules warrant short-term, high-dose treatment for targeting the tumour growth, and long-term, low-dose treatment for targeting the invasion of osteosarcoma.
authors.affiliation: lst Institute of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, H-1085, 26 Ulloiút, Budapest, Hungary.
authors.forename: Revekka
authors.initials: R
authors.lastname: Harisi
authors.forename: József
authors.initials: J
authors.lastname: Dudás
authors.forename: Ferenc
authors.initials: F
authors.lastname: Tímár
authors.forename: Gábor
authors.initials: G
authors.lastname: Pogány
authors.forename: Sándor
authors.initials: S
authors.lastname: Paku
authors.forename: József
authors.initials: J
authors.lastname: Tímár
authors.forename: Ilona
authors.initials: I
authors.lastname: Kovalszky
authors.forename: Miklós
authors.initials: M
authors.lastname: Szendroi
authors.forename: András
authors.initials: A
authors.lastname: Jeney
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D019012:Integrin beta1; D004317:Doxorubicin; D020782:Matrix Metalloproteinases; D004250:DNA Topoisomerases, Type II