Antiproliferative and antimigratory effects of doxorubicin in human osteosarcoma cells exposed to extracellular matrix

Revekka Harisi, József Dudás, Ferenc Tímár, Gábor Pogány, Sándor Paku, József Tímár, Ilona Kovalszky, Miklós Szendroi, András Jeney

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 β1 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 μg/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.

Original languageEnglish
Pages (from-to)805-813
Number of pages9
JournalAnticancer research
Volume25
Issue number2 A
Publication statusPublished - Mar 1 2005

Keywords

  • Doxorubicin
  • Extracellular matrix
  • Matrix-metalloproteinase
  • Migration
  • Osteosarcoma
  • Proliferation
  • Topoisomerase II
  • β1 integrin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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