Altered Morphology, Nuclear Stability and Adhesion of Highly Metastatic Derivatives of Osteoblast-like SAOS-2 Osteosarcoma Cells

Abstract

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.