Osteosarcoma and Metastasis Associated Bone Degradation—A Tale of Osteoclast and Malignant Cell Cooperativity

Abstract

Cancer-induced bone degradation is part of the pathological process associated with both primary bone cancers, such as osteosarcoma, and bone metastases originating from, e.g., breast, prostate, and colon carcinomas. Typically, this includes a cancer-dependent hijacking of processes also occurring during physiological bone remodeling, including osteoclast-mediated disruption of the inorganic bone component and collagenolysis. Extensive research has revealed the significance of osteoclast-mediated bone resorption throughout the course of disease for both primary and secondary bone cancer. Nevertheless, cancer cells representing both primary bone cancer and bone metastasis have also been implicated directly in bone degradation. We will present and discuss observations on the contribution of osteoclasts and cancer cells in cancer-associated bone degradation and reciprocal modulatory actions between these cells. The focus of this review is osteosarcoma, but we will also include relevant observations from studies of bone metastasis. Additionally, we propose a model for cancer-associated bone degradation that involves a collaboration between osteoclasts and cancer cells and in which both cell types may directly participate in the degradation process.

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvβ3 Axis

“…Osteosarcoma is associated with high rates of pulmonary metastasis [ 1 ]. The prognosis for patients with pulmonary metastasis is worse than for those with localized disease, characterized by substantially reduced survival [ 3 ].…”

“…Osteosarcoma, the most common primary bone malignancy, is renowned for its high propensity for metastasis [ 1 ]. As many as 20% of patients present with lung metastases at their initial diagnosis; around 40% of patients develop metastases after their initial presentation despite the best available treatment [ 2 ].…”

“…As many as 20% of patients present with lung metastases at their initial diagnosis; around 40% of patients develop metastases after their initial presentation despite the best available treatment [ 2 ]. Whereas 5-year overall survival is around 50–80% in patients with localized osteosarcoma [ 1 ], only 27% of patients with metastatic disease survive longer than 5 years [ 3 ]. No agents exist that can successfully cure metastatic osteosarcoma, so it is essential that such treatment is developed [ 4 ].…”

Extracellular Vesicles in Osteosarcoma: Antagonists or Therapeutic Agents?

“…At the same time, osteoclast bone resorption can lead to the release of pro-tumor factors as IGF-1 (Insulin Growth Factor 1) and TGF-β from the bone matrix that stimulate tumor cells [50,51]. The role of osteoclasts in the onset and progression of osteosarcoma is still controversial [52,53]. There are clinical and experimental data showing that the presence of osteoclasts in osteosarcoma-adjacent tissue is associated with poor outcomes [52], but on the other hand, published studies suggest that the presence of osteoclasts at the primary site of OS lesions prevents metastasis [52,54].…”

“…The role of osteoclasts in the onset and progression of osteosarcoma is still controversial [52,53]. There are clinical and experimental data showing that the presence of osteoclasts in osteosarcoma-adjacent tissue is associated with poor outcomes [52], but on the other hand, published studies suggest that the presence of osteoclasts at the primary site of OS lesions prevents metastasis [52,54]. Endo-Munoz et al found that expression of osteoclast-specific tartrate-resistant acid phosphatase 5 (TRAcP5) is significantly downregulated in biopsies isolated from osteosarcoma patients compared with nonmalignant bone tissue.…”