Magnetically Empowered Malignant Tumor Cells As Micro-Living Motors to Construct a Bone Original or Bone Metastasis Human-Mouse Chimera Tumor Model

Background

The important premise of exploring the occurrence and development mechanism of hematopoietic maligances (AML,ALL,MM, etc.), which called bone original tumors, and (lung cancer, liver cancer etc.) bone metastasis is to construct a good animal model of bone metastasis. At present, tumor bone metastasis models can be established by caudal artery injection (IA),caudal vein injection and bone marrow cavity injection (IBM), but all of the above models have the defects of low bone metastasis rate, low specificity and short survival time in mice. By empowering hematopoietic maligances and solid tumor cells with magnetical Taqs, combined with a precise magnetic field in the bone, such tumor cells can be changed into Magnetically Empowered Cancer cells (MEC) with specific biological characters.

Aims

To construct a bone original or bone metastasis chimera model in immunodeficiency mice with MEC, then examine the model for further research with fixed point, quantitative, high specificity and high consistency.

Method

Explore the biological characteristics of Magnetically empowered GFP⁺Luc⁺NCI-H929 (Multiple Myeloma cellline, ME-GL-NCI-H929) and GFP⁺Luc⁺A549 (lung cancer cellline, ME-GL/A549) in vitro. In vivo chimeric models of multiple myeloma model and bone metastasis of lung cancer in human and mice were established by IA, IBM, and bone marrow cavity injection with external magnetic field (IBM-M). The time and size of multiple myeloma and bone tumorigenesis, metastasis of other organs and tumorigenesis rate in the three groups were compared by small animal in vivo imaging system, micro-CT, MRI, pathology, morphology and other experimental methods.

Results

Compared with GL-NCI-H929 vs ME-GL-NCI-H929 and GL-A549 vs ME-GL-A549 had no significant difference in biological characteristics such as proliferation and apoptosis(P>0.05). The tumor formation rate of IBM-M group was significantly higher than that of IA group and IBM group(P<0.05). The formation of IBM-M was rapid, the tumor was homogeneous and limited to the bone of the injection side, and there was no metastasis of important organs in vivo. The tumor in IA group and IBM group is unstable and has metastasis of other organs.

Conclusion

We reported the accurate modeling technology of magnetic induced cells for the first time, which has the advantages of high tumor formation rate, high specificity, strong model consistency, long observation window period and so on. This method has successfully constructed multiple myeloma as well as lung cancer bone metastasis human-mouse chimera model, which provides convenience for the study of related disease diagnosis and treatment mechanism and has a wide range of applications.

No relevant conflicts of interest to declare.