Abstract
Malignant melanoma favors spreading to bone, resulting in a weakened bone with a high fracture risk. Here, we revealed the disorganized alignment of apatite crystals in the bone matrix associated with the homing of cancer cells by developing an artificially controlled ex vivo melanoma bone metastasis model. The ex vivo metastasis model reflects the progressive melanoma cell activation in vivo, resulting in decreased bone mineral density and expression of MMP1-positive cells. Moreover, less organized intercellular connections were observed in the neighboring osteoblasts in metastasized bone, indicating the abnormal and randomized organization of bone matrix secreted by disconnected osteoblasts. Our study revealed that the deteriorated microstructure associated with disorganized osteoblast arrangement was a determinant of malignant melanoma-related bone dysfunction.
Highlights
The malignant melanoma bone metastasis model was successfully established by the controlled culturing of embryonic bone tissue inside a static uniaxial loading platform
Immunohistochemical analysis demonstrated that coculture with malignant melanoma cells induced a high expression of melan A and matrix metalloprotease1 (MMP1), in spite that the background staining is slightly detected in control bone (Figure 2)
The results indicate that the established melanoma metastasis model accurately reflects the biological events induced by malignant melanoma invasion
Summary
Malignant melanoma is one of the progressive cancers favoring bone metastasis, and its invasion of bone results in severe skeletal deterioration [1]. Bone metastasis is generally classified into osteoblastic or osteolytic metastasis based on the radiographic diagnosis of the balance between bone formation and resorption [2]. Prostate cancer or breast cancer promotes or suppresses bone formation, respectively, thereby influencing the development of bone diseases. Malignant melanoma cases present multiple types of pathological defects, and its effects on bone cell activities vary depending on the progressive stages of melanoma [3]. While the bony invasion and homing processes of malignant melanoma cells comprises complicated molecular regulation of cancer-bone crosstalk, the essential biological events triggering bone dysfunction related to melanoma metastasis are poorly understood
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