Early TGF-β inhibition in mice reduces the incidence of breast cancer induced bone disease in a myeloid dependent manner

Bone
Denise BuenrostroJulie A Sterling

Abstract

The tumor-cell microenvironment is recognized as a dynamic place where critical cell interactions occur and play an important role in altering tumorigenesis. While many studies have investigated the effects of cellular cross-talk within distinct tumor microenvironments, these interactions have yet to be fully examined in bone. It is well-established that many common cancers metastasize to bone, resulting in the development of tumor-induced bone disease (TIBD), a multi-facetted illness that is driven by complex cell interactions within the bone marrow. Our group has previously published that myeloid progenitor cells expand in the presence of tumors in bone, aligning with the notion that myeloid cells can act as tumor promotors. Several groups, including ours, have established that transforming growth factor β (TGF-β), an abundant growth factor in bone, can regulate both TIBD and myeloid expansion. TGF-β inhibitors have been shown to increase bone volume, decrease bone destruction, and reduce but not eliminate tumor. Therefore, we hypothesize that inhibiting TGF-β will reduce myeloid expansion leading to a reduction of tumor burden in bone and osteoclast-mediated bone loss, causing to an overall reduction in TIBD. To address this...Continue Reading

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Citations

Oct 16, 2018·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Julia Paton-HoughMichelle A Lawson
Jan 16, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kenneth M Kozloff
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May 1, 2021·International Journal of Molecular Sciences·Julia N ChengJanet L Funk

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