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Osteoblasts in prostate cancer metastasis to bone

Key Points

  • Patients with advanced prostate cancer frequently develop bone metastases.

  • The tropism of prostate cancer cells for bone and their tendency to induce the osteoblastic phenotype is a result of interactions between prostate cancer cells and osteoblasts. Prostate cancer cells might depend on an osteoblast-derived factor for their growth.

  • Prostate cancer cells produce factors that perturb the bone microenvironment in ways that affect the normal functional balance between osteoblast and osteoclast activities, resulting in osteoblastic metastases.

  • Osteoblasts also secrete factors that facilitate progression of prostate cancer in bone.

  • Therapeutics designed to target the interaction between prostate cancer and osteoblasts might prevent or treat prostate cancer bone metastases.

Abstract

Metastasis to bone is common in lung, kidney, breast and prostate cancers. However, prostate cancer is unique in that bone is often the only clinically detectable site of metastasis, and the resulting tumours tend to be osteoblastic (bone forming) rather than osteolytic (bone lysing). The interaction between host cells and metastatic cancer cells is an important component of organ-specific cancer progression. How can this knowledge lead to the development of more effective therapies?

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Figure 1: Role of osteoblasts and osteoclasts in bone remodelling.
Figure 2: Signal-transduction pathways that regulate osteoblast function.
Figure 3: Prostate cancer cell and osteoblast interaction.

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Acknowledgements

We thank L.-Y. Yu-Lee, J. Kim and S.-M. Tu for helpful comments.

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Correspondence to Christopher J. Logothetis or Sue-Hwa Lin.

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DATABASES

Entrez Gene

BMP2

ET1

IGF1

IGF2

IGFBP3

LRP5

osteocalcin

osteoprotegerin

PDGF

PSA

PTHRP

RANKL

RUNX2

TGFβ1

TGFβ2

uPA

VEGF

WNT1

National Cancer Institute

breast cancer

kidney cancer

lung cancer

multiple myeloma

prostate cancer

FURTHER INFORMATION

Advances in the treatment of metastatic prostate cancer

Bone tumour information source

eMedicine article on prostate cancer

Management of metastatic prostate cancer

Metastatic bone disease

Prostate cancer staging

Glossary

HEMIPARESIS

Complete loss of muscle strength involving one side of the body.

PARESIS

Complete loss of muscle strength on both sides of the body.

BISPHOSPHONATES

A class of drugs used to strengthen bone by inhibiting osteoclast bone resorption.

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Logothetis, C., Lin, SH. Osteoblasts in prostate cancer metastasis to bone. Nat Rev Cancer 5, 21–28 (2005). https://doi.org/10.1038/nrc1528

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