Understanding the Bone in Cancer Metastasis

Abstract

The bone is the third most common site of metastasis for a wide range of solid tumors including lung, breast, prostate, colorectal, thyroid, gynecologic, and melanoma, with 70% of metastatic prostate and breast cancer patients harboring bone metastasis. (1) Unfortunately, once cancer spreads to the bone, it is rarely cured and is associated with a wide range of morbidities including pain, increased risk of fracture, and hypercalcemia. This fact has driven experts in the fields of bone and cancer biology to study the bone, and has revealed that there is a great deal that each can teach the other. The complexity of the bone was first described in 1889 when Stephen Paget proposed that tumor cells have a proclivity for certain organs, where they "seed" into a friendly "soil" and eventually grow into metastatic lesions. Dr. Paget went on to argue that although many study the "seed" it would be paramount to understand the "soil." Since this original work, significant advances have been made not only in understanding the cell-autonomous mechanisms that drive metastasis, but also alterations which drive changes to the "soil" that allow a tumor cell to thrive. Indeed, it is now clear that the "soil" in different metastatic sites is unique, and thus the mechanisms that allow tumor cells to remain in a dormant or growing state are specific to the organ in question. In the bone, our knowledge of the components that contribute to this fertile "soil" continues to expand, but our understanding of how they impact tumor growth in the bone remains in its infancy. Indeed, we now appreciate that the endosteal niche likely contributes to tumor cell dormancy, and that osteoclasts, osteocytes, and adipocytes can impact tumor cell growth. Here, we discuss the bone microenvironment and how it impacts cancer cell seeding, dormancy, and growth. Fig. 1. Tumor cells closely associate with cells of the bone microenvironment in a mouse model of bone metastasis. Scale bar ¼ 50 mm. Ad ¼ adipocyte; EC ¼ endothelial cell; Oc ¼ osteocyte; Ocl ¼ osteoclast; Tu ¼ tumor.

Prostate Cancer Phenotype Influences Bone Mineralization at Metastasis: A Study Using an In Vitro Prostate Cancer Metastasis Testbed

“…The interaction between prostate cancer and the bone microenvironment has been an important research emphasis for years because of the characteristic preference of prostate cancer cells to metastasize to bone . One of the significant barriers for investigating the osteotropic nature of prostate cancer cells has been the lack of availability of an appropriate in vitro model that mimics closely the in vivo bone microenvironment in response to bone–cancer interaction.…”

“…The interaction between prostate cancer and the bone microenvironment has been an important research emphasis for years because of the characteristic preference of prostate cancer cells to metastasize to bone. (9) One of the significant barriers for investigating the osteotropic nature of prostate cancer cells has been the lack of availability of an appropriate in vitro model that mimics closely the in vivo bone microenvironment in response to bone-cancer interaction. In recent years, with the development of 3D in vitro models as tools for investigating the molecular mechanism of cancer metastasis, a significant number of novel and innovative 3D models has been reported in an attempt to recapitulate the native tumor microenvironment.…”

Peptide targeting of the lysolipid-sensing GPR55 for osteoclastogenesis tuning

“…Peptide-P1 was also shown to inhibit GPR55-dependent proliferation of EHEB and DeFew cells, which are two human B-lymphoblastoid cell lines [38], and among other tumour cells, leukemic cells can metastasise at the bone level [63]. Bone metastasisation is a complex process that involves cross-talk between tumour cells and bone resident cells [64,65]. Osteoclast bone resorption is essential for metastasis establishment, as upon bone degradation, growth factors are released from the bone matrix that can stimulate metastatic cell growth and survival [66].…”

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

“…Metastasis is the spread of cancer cells from a primary tumor to distant sites to create secondary tumors. It is a stage of the disease usually considered to be incurable with mainly palliative treatments [92]. Its origin is the pre-metastatic niche, which is an environment in a secondary organ induced by the primary cancer cells that provides favorable conditions for the growth of tumoral cells [93].…”