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. 2024 May 17:47:100610.
doi: 10.1016/j.jbo.2024.100610. eCollection 2024 Aug.

Emerging roles for stromal cells in bone metastasis

Karl J Nyman  1   2 , Jeremy S Frieling  2 , Conor C Lynch  2
Affiliations

Emerging roles for stromal cells in bone metastasis

Karl J Nyman et al. J Bone Oncol. .

Abstract

The skeleton is a common site of cancer metastasis and malignancy with the resultant lesions often being incurable. Interactions between metastatic cancer cells and the bone microenvironment are critical for cancer cell survival, outgrowth, and progression. Mesenchymal Stem Cells (MSCs) are an essential stromal cell type in bone that are appreciated for their impacts on cancer-induced bone disease, however, newer evidence suggests that MSCs possess extensive roles in cancer-bone crosstalk, including cancer cell dormancy, metabolic demands, and immune-oncology. Emerging evidence has also identified the importance of MSC tissue source and the influence of ageing when studying MSC biology. Combining these considerations together with developing technologies such as spatial transcriptomics will contribute to defining the molecular mechanisms underlying complex stroma-cancer interactions in bone and assist with identification of therapeutically tractable targets.

Keywords: Bone; Bone metastasis; MSC; Mesenchymal stem cell; Microenvironment; Stromal cell.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Emerging areas for mesenchymal stem cells (MSCs) in bone metastasis. 1) MSCs can maintain dormancy in breast cancer cells via TGFβ2 and BMP7, but also induce proliferation of dormant cancer cells via N-cadherin. 2) Cancer cells rewire metabolism of MSCs and other stromal cells, impairing normal hematopoiesis while facilitating cancer cell survival, proliferation, and chemoresistance via transfer of reactive oxygen species (ROS), organelles, and amino acids such as glutamine. 3) Age-related changes in MSCs have profound effects on cancer progression by increased senescence, secretion of senescence associated secretory phenotypes (SASP) factors, and increased bone marrow adipocytes. 4) Immunomodulatory roles of MSCs include inhibitory effects via adhesion molecules and release of TGFβ and HGF, but engineering MSCs to deliver cargo, such as IL-7 and IL-12, offers improved efficacy of CAR-T cells. Figure created with BioRender.com.
See this image and copyright information in PMC

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