Abstract
BackgroundTo study the effects of zoledronic acid (ZA) on the vasculogenic mimicry of osteosarcoma cells in vitro.MethodsA Three-dimensional culture of LM8 osteosarcoma cells on a type I collagen matrix was used to investigate whether osteosarcoma cells can develop vasculogenic mimicry, and to determine the effects of ZA on this process. In addition, the cellular ultrastructural changes were observed using scanning electron microscopy and laser confocal microscopy. The effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells were measured via immunoblotting.ResultsZA inhibited the development of vasculogenic mimicry by the LM8 osteosarcoma cells, decreased microvilli formation on the cell surface, and disrupted the F-actin cytoskeleton. ZA prevented translocation of RhoA protein from the cytosol to the membrane in LM8 cells.ConclusionsZA can impair RhoA membrane localization in LM8 cells, causing obvious changes in the ultrastructure of osteosarcoma cells and induce cell apoptosis, which may be one of the underlying mechanisms by which the agent inhibits the development of vasculogenic mimicry by the LM8 cells.
Highlights
To study the effects of zoledronic acid (ZA) on the vasculogenic mimicry of osteosarcoma cells in vitro
The results showed that 5 μmol/L ZA induced extensive apoptosis, while there were only a few apoptotic cells present in the control group
ZA prevents RhoA membrane localization in LM8 cells Since the small GTPase RhoA must be targeted to the plasma membrane for its activation, we examined the effects of ZA on the translocation of RhoA protein from the cytosol to the membrane in LM8 cells after separation of cytosolic and membrane fractions
Summary
To study the effects of zoledronic acid (ZA) on the vasculogenic mimicry of osteosarcoma cells in vitro. Solid malignant tumors require a robust blood supply to support growth and metastasis. In 1999, Maniotis et al discovered a new type of blood vessel in human malignant uveal melanoma [1]. The blood vessel walls were created by deformed malignant melanoma cells and stromal cells. Because their structure was similar to regular blood vessels, they were considered to have vasculogenic mimicry (VM). Subsequent research found that tumors that harbor VM, such as malignant melanoma, synovial sarcoma, mesothelial sarcoma, and ovarian cancer, possess the following characteristics: a high degree of malignancy, uncommitted differentiation or bi-directional differentiation status, rapid growth, and a high rate of metastasis [2,3,4,5]
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