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Key mechanism of bone destruction in melanoma bone destruction identified

Writer's picture: Derm CityDerm City


Photo by: MAKY.OREL via Wikimedia Commons
Photo by: MAKY.OREL via Wikimedia Commons

Researchers have identified ferroptosis as the primary mechanism driving osteocyte death in melanoma bone metastasis, offering the possibility of a new approach to treatment for patients with this aggressive form of skin cancer. The study, published in Bone Research on Jan. 16, 2025, outlines some of the complex interactions between melanoma cells and the bone microenvironment, potentially paving the way for exploration of novel therapies.


The researchers from Friedrich-Alexander-University Erlangen-Nürnberg in Erlangen, Germany noted that melanoma frequently metastasizes to bones, leading to severe bone loss, increased fracture risk, and significant pain. This bone metastasis is associated with poor survival rates and a markedly reduced quality of life for patients. Osteocytes, the most abundant cells in bone, play an important role in maintaining bone structure and regulating bone remodelling, but their role in bone destruction during melanoma metastasis has been unknown.


In the study, the researchers used in vivo and in vitro models to investigate the mechanisms underlying osteocyte death. Their findings revealed that melanoma cells induce ferroptosis in osteocytes through the upregulation of HMOX1, a gene involved in iron metabolism and heme oxidation.


The activation of the HIF1α-HMOX1 axis was found to drive excessive autophagy and ferritin degradation, leading to intracellular iron overload and lipid peroxidation–which are hallmarks of ferroptosis.


The HIF1α pathway was shown as an upstream regulator, providing a potential target for modulating HMOX1 expression and influencing autophagy-dependent ferroptosis. When HMOX1 was inhibited with the specific inhibitor Znpp, osteocyte death was significantly reduced and bone integrity was preserved. When compared, the classical ferroptosis inhibitor Fer-1 had a lesser effect, the authors noted.


Dr. Aline Bozec, the study’s lead investigator, emphasized the significance of these findings in a press release:


“Our research offers a deeper understanding of the intricate interactions between melanoma cells and the bone microenvironment. By identifying the HIF1α-HMOX1 axis as a key driver of osteocytes ferroptosis, we have uncovered a promising therapeutic target that could have a profound impact on the treatment of bone metastasis.”


The discovery of ferroptosis as a driver of osteocyte death in melanoma bone metastasis has broad implications for clinical treatment, the researchers reported. Targeting the HIF1α-HMOX1 axis could offer a novel approach to reduce osteocyte death and preserve bone integrity, potentially improving the prognosis for melanoma patients with bone metastasis.


The authors believe this research strategy may be extended to other cancers that commonly metastasize to the bone, potentially providing new avenues for treatment for those cancer types as well.

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