Abstract
The bone microenvironment is an ideal fertile soil for both primary and secondary tumors to seed. The occurrence and development of osteosarcoma, as a primary bone tumor, is closely related to the bone microenvironment. Especially, the metastasis of osteosarcoma is the remaining challenge of therapy and poor prognosis. Increasing evidence focuses on the relationship between the bone microenvironment and osteosarcoma metastasis. Many elements exist in the bone microenvironment, such as acids, hypoxia, and chemokines, which have been verified to affect the progression and malignance of osteosarcoma through various signaling pathways. We thoroughly summarized all these regulators in the bone microenvironment and the transmission cascades, accordingly, attempting to furnish hints for inhibiting osteosarcoma metastasis via the amelioration of the bone microenvironment. In addition, analysis of the cross-talk between the bone microenvironment and osteosarcoma will help us to deeply understand the development of osteosarcoma. The cellular and molecular protagonists presented in the bone microenvironment promoting osteosarcoma metastasis will accelerate the exploration of novel therapeutic strategies towards osteosarcoma.
Highlights
The bone microenvironment is composed of bone marrow and a mineralized extracellular matrix
We reviewed the promoting effect of the main components in the bone microenvironment on OS metastasis such as mesenchymal stem cells, hypoxia, acidosis, and chemokine
Previous studies showed that the bone microenvironment promotes the OS metastasis or malignancy
Summary
The bone microenvironment is composed of bone marrow and a mineralized extracellular matrix. We reviewed the promoting effect of the main components in the bone microenvironment on OS metastasis such as mesenchymal stem cells, hypoxia, acidosis, and chemokine. Malignant OS cells form a complex mixture with other normal cells (MSCs, fibroblasts, osteoblasts, and myeloid immune cells) and some chemical factors (hypoxia, acidosis). This special tumor microenvironment of the complex mixture is a perfect place for OS to develop and metastasize. Understanding this special bone microenvironment, the mechanism of OS metastasis can be better understood, and it is possible to find a therapeutic target for the treatment of OS metastasis
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