[Frontiers in Bioscience S2, 907-915, June 1, 2010]

Osteomimicry: how tumor cells try to deceive the bone

Nadia Rucci , Anna Teti

Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

TABLE OF CONTENTS

1. Abstract
2. The metastasis process
3. Bone as preferential site of metastasis
4. Osteomimicry
4.1. Osteomimicry in osteolytic bone metastases
4.2. Osteomimicry in osteoblastic bone metastases
4.2.1. Urokinase-type plasminogen activator (uPA)
4.2.2. Endothelin 1 (ET-1)
4.2.3. Beta2-Microglobulin (Beta2-M)
4.3. Key molecules of tumor osteomimicry
4.3.1. Bone matrix proteins
4.3.2. Runt-related transcription factor 2 (Runx2)
4.3.3. Bone Morphogenetic Proteins (BMPs)
4.3.4. Wnt signaling
5. Conclusions and future perspectives
6. References

1. ABSTRACT

Bone metastases are complications of multiple myeloma and solid tumors, including breast and prostate carcinomas. Several reports have demonstrated that the preference to metastasize to bone by tumor cells is not a casual but an addressed event, which relies on specific interactions among tumor cells, bone marrow microenvironment and bone cells. One of the features that gives tumor cells more chances to survive and proliferate into the bone tissue is osteomimicry, that is the ability to acquire a bone cell phenotype, especially osteoblast-like. As clearly demonstrated, prostate and breast cancer cells try to resemble osteoblasts by expressing bone matrix proteins, the specific marker alkaline phosphatase, and molecules regulating the osteoblast/osteoclast cross-talk. Based on this evidence it is crucial to dissect in more detail the molecular mechanisms underlying the osteomimetic properties of cancer cells and identify new therapeutic targets eventually leading to a better and prolonged life expectation for patients with bone