Bone microenvironment signals in osteosarcoma development

Abstract

The bone is a complex connective tissue composed of many different cell types such as osteoblasts, osteoclasts, chondrocytes, mesenchymal stem/progenitor cells, hematopoietic cells and endothelial cells, among others. The interaction between them is finely balanced through the processes of bone formation and bone remodeling, which regulates the production and biological activity of many soluble factors and extracellular matrix components needed to maintain the bone homeostasis in terms of cell proliferation, differentiation and apoptosis. Osteosarcoma (OS) emerges in this complex environment as a result of poorly defined oncogenic events arising in osteogenic lineage precursors. Increasing evidence supports that similar to normal development, the bone microenvironment (BME) underlies OS initiation and progression. Here, we recapitulate the physiological processes that regulate bone homeostasis and review the current knowledge about how OS cells and BME communicate and interact, describing how these interactions affect OS cell growth, metastasis, cancer stem cell fate and therapy outcome.

The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma

“…Osteosarcomas are bone-forming tumors characterized by the presence of an extracellular osteoid matrix produced by cancer cells and associated with a very complex local environment including bone cells, blood vessels, stromal cells and immune infiltrates [3][4][5][6]. The osteosarcoma cell is the tumorous counterpart of osteoblast.…”

“…Indeed, based on the "seed and soil' theory of Paget, it is now well recognized that osteosarcoma, like other cancers, requires an adequate local microenvironment for its development [11,12]. This microenvironment can provide all metabolites and factors for the control of proliferation, drug resistance, dissemination or/and dormancy of osteosarcoma cells [5,[13][14][15]. Then, the pressure exerted by microenvironment may be responsible for a specific selection of osteosarcoma cells with predominant specificities such as a high quiescent or a proliferative profile.…”

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

“…MSCs are a heterogeneous subpopulation of adult stem cells with immunomodulatory properties and a potential to diferentiate into several tissue-speciic cells such as OBs, adipocytes, and chondrocytes [121].…”

Osteogenic Sarcoma: A 21st Century Review

“…The fact that the defining feature of BOS is the production of osteoid by the tumor cells gives the impression that the primary cell of origin is the osteoblast, a cell with mesenchymal germline origin. It is also a known fact that the tumor microenvironment contributes significantly to the diagnostic definition and tumor development in each of the subtypes (16). Thus, Mutsaers and Walkley raised important questions about the cell of origin based on the apparent heterogeneity of whether the disease arises from a single cell type or different cell types.…”