Document Detail


Altered morphology, nuclear stability and adhesion of highly metastatic derivatives of osteoblast-like SAOS-2 osteosarcoma cells.
MedLine Citation:
PMID:  18225558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Metastasis is the leading cause of death in patients with osteosarcoma (OS). High alkaline phosphatase (ALP) activity and resistance to chemotherapy are independent predictors of poor clinical outcome of osteosarcoma. Here, the osteoblastic phenotype, cell and nuclear morphology, cell adhesion and drug resistance of the SAOS-2 cell line and two in vivo selected highly metastatic derivatives, LM5 and LM7, were compared. RESULTS: ALP activity and deposition of mineralized extracellular matrix were the same in the parental SAOS-2 and the LM5 and LM7 cells, but parathyroid hormone (PTH)-stimulated cAMP accumulation was lost in the LM7 cells. The LM5 and LM7 cells were smaller than the parental SAOS-2 cells, and 10% of the LM7 cells had distorted nuclei. The adhesion of LM5 and LM7 cells was decreased when compared to SAOS-2 cells. The cytotoxic responses of the SAOS-2, LM5 and LM7 cells to Cisplatin, Doxorubicin and Etoposide were indistinguishable. CONCLUSION: The increased metastatic potential of LM5 and LM7 as compared to SAOS-2 cells is not associated with a substantial change of the osteoblastic phenotype or of the cytotoxic response to current chemotherapeutic drugs. The decrease in cell size and altered cell adhesion, reflecting cytoskeletal rearrangement, together with increased nuclear instability and partial dedifferentiation, as revealed by the loss of PTH responsiveness in LM7 cells, may account for the higher metastatic potential of the LM5 and LM7 sublines as compared to the parental SAOS-2 cells.
Authors:
Roman Muff; Natalie Nigg; Philipp Gruber; Denise Walters; Walter Born; Bruno Fuchs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  27     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2007 Nov-Dec
Date Detail:
Created Date:  2008-01-29     Completed Date:  2008-02-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3973-9     Citation Subset:  IM    
Affiliation:
Laboratory for Orthopaedic Research, Department of Orthopaedics, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Alkaline Phosphatase / metabolism
Bone Neoplasms / drug therapy,  metabolism,  pathology*
Cell Adhesion / physiology
Cell Line, Tumor
Cell Nucleus / pathology
Cisplatin / pharmacology
Cyclic AMP / biosynthesis
Doxorubicin / pharmacology
Drug Resistance, Neoplasm
Etoposide / pharmacology
Humans
Neoplasm Invasiveness
Osteoblasts / pathology
Osteosarcoma / drug therapy,  metabolism,  pathology*
Chemical
Reg. No./Substance:
15663-27-1/Cisplatin; 23214-92-8/Doxorubicin; 33419-42-0/Etoposide; 60-92-4/Cyclic AMP; EC 3.1.3.1/Alkaline Phosphatase

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