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.
Highlights
Bone cancer can occur due to the development of primary bone tumors or as the result of metastasis formation by disseminated cancer cells from distant organs
As in physiological bone development and homeostasis, the osteoclast is considered the main player when it comes to bone degradation in primary bone cancer, and it plays an intricate role in tumor progression
Dysregulated bone remodeling, resulting in pathological bone degradation, is a devastating consequence of bone cancer, it appears to be an essential component of bone cancer development
Summary
Bone cancer can occur due to the development of primary bone tumors or as the result of metastasis formation by disseminated cancer cells from distant organs. Bone is the third most common site for metastasis in general, but with considerable variation between cancer types It is most prominent in patients with prostate cancer, of which 30% develop bone metastases within 10 years after diagnosis of the primary tumor, followed by 13% of lung cancer patients, 10% of renal cancer patients, 8% of breast cancer patients, and 3% of colorectal and malignant melanoma patients [3]. Based on data from a Danish cohort study, Svensson and colleagues reported that in the period from 1994 to 2012 the 5-year survival rate after diagnosis of bone metastasis was only 1% for lung cancer, 3% for colon cancer, 5% for kidney and melanoma, 6% for prostate cancer, and 13% for breast cancer [7]. We will discuss indications of direct bone-degradation actions mediated by the malignant cells and propose a model that encompasses a cooperation between osteoclasts and cancer cells, which is distinct from that of the vicious cycle model
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