Hanna Taipaleenmäki
Institute of Musculoskeletal Medicine, Musculoskeletal University Center Munich, Planegg, Germany
Beyond the Vicious Cycle: Microenvironmental Control of Bone Metastasis
Bone is one of the most frequent sites of metastasis in advanced cancer, where metastatic lesions cause major morbidity through pain, fractures, hypercalcemia, and bone marrow dysfunction. Bone metastasis has classically been described through the concept of a “vicious cycle,” in which bone remodeling is disrupted by tumor cells, leading to osteolysis and the release of growth-promoting factors that further support metastatic progression. Although this framework remains influential, the cellular and molecular complexity of the bone metastatic niche is not fully captured by this model. In this seminar, new roles for osteoblast-lineage cells and osteoclasts will be discussed, with emphasis on how metastatic outgrowth is shaped by the bone microenvironment. Interactions between tumor cells and bone-resident remodeling compartments will be highlighted, as well as their roles in regulating niche architecture and creating therapeutically exploitable vulnerabilities. By revisiting the vicious cycle from a broader microenvironmental perspective, new insights into the mechanisms that drive bone metastasis and potential strategies for intervention will be presented.
Selected references
- Maeda M, Saito H, Ribet ABP, Hesse E, Taipaleenmäki H. Tgif1-deficiency impairs osteoclast differentiation through PP2A-mediated ERK1/2 dephosphorylation and attenuates bone loss in mice. J Bone Miner Res. 2025
- Bolamperti S, Saito H, Heerdmann S, Hesse E, Taipaleenmäki H. Tgif1-deficiency impairs cytoskeletal architecture in osteoblasts by activating PAK3 signaling. Elife. 2024 Apr 25;13:RP94265
- Taipaleenmäki H, Saito H, Schröder S, Maeda M, Mettler R, Ring M, Rollmann E, Gasser A, Haasper C, Gehrke T, Weiss A, Grimm SK, Hesse E. Antagonizing microRNA-19a/b augments PTH anabolic action and restores bone mass in osteoporosis in mice. EMBO Mol Med. 2022 Nov 8;14(11):e13617
- Hesse E, Schröder S, Brandt D, Pamperin J, Saito H, Taipaleenmäki H. Sclerostin inhibition alleviates breast cancer-induced bone metastases and muscle weakness. JCI Insight. 2019 Apr 9;5(9):e125543