Platelet-derived lysophosphatidic acid supports the progression of osteolytic bone metastases in breast cancer

Boucharaba, Ahmed; Serre, Claire-Marie; Grès, Sandra; Saulnier-Blache, Jean Sébastien; Bordet, Jean‐Claude; Guglielmi, Julien; Clézardin, Philippe; Peyruchaud, Olivier

doi:10.1172/jci22123

Cited by 184 publications

(111 citation statements)

References 45 publications

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“…TGF-β and platelet-derived lysophosphatidic acid (LPA), also secreted by platelets, promote osteoclastic activation and bone resorption (Fig. 3) [68, 69]. The ‘‘vicious cycle’’ described offers a strong foundation for therapeutic intervention.…”

Section: Mechanisms Of Osteolytic Metastasesmentioning

confidence: 99%

Molecular Regulation of Bone Metastasis Pathogenesis

Yiang

et al. 2018

Cell Physiol Biochem

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Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions. Studies support the idea that distant metastases may occur due to the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These cells inhibit T cells and natural killer (NK) cells and differentiate into tumor-associating macrophages (TAMs), monocytes, and dendritic cells (DCs). In this review, we summarize studies focusing on the role of MDSCs in bone metastasis and provide a strong foundation for developing anticancer immune treatments and anticancer therapies, in general.

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Section: Mechanisms Of Osteolytic Metastasesmentioning

confidence: 99%

Molecular Regulation of Bone Metastasis Pathogenesis

Yiang

et al. 2018

Cell Physiol Biochem

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“…LPA levels are reduced in rats by antibody-mediated thrombocytopenia or treatment of mice with a platelet integrin inhibitor that also induces thrombocytopenia (7,14). Platelet-derived microparticles have also been cited as a source for the generation of LPA (9).…”

Section: Circulating Lpa Levelsmentioning

confidence: 99%

Lysophosphatidic Acid (LPA) Signaling and Cardiovascular Pathology

Smyth

Dong

Wheeler

et al. 2013

Lysophospholipid Receptors

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“…Forced overexpression of LPA 1 in human MDA-B02 breast carcinoma cells leads to an increase in the capacity of these cells to induce bone metastases when injected intravenously into athymic (nude) mice (11). In vitro, overexpression of LPA 1 sensitizes specifically these cells to the mitogenic action of LPA and increases tumor cell secretion of a panel of cytokines known to control osteoclast activity (IL-6, IL-8, GM-CSF, Groα, MCP1) (11,12). These results strongly correlate with in vivo observations showing increased cancer cell proliferation and bone loss in animals bearing bone metastases.…”

Section: Lpa Signaling In Osteolytic Bone Metastasesmentioning

confidence: 99%