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The type 1 lysophosphatidic acid receptor is a target for therapy in bone metastases

机译:1型溶血磷脂酸受体是骨转移治疗的靶标

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摘要

Platelet-derived lysophosphatidic acid (LPA) supports the progression of breast and ovarian cancer metastasis to bone. The mechanisms through which LPA promotes bone metastasis formation are, however, unknown. Here we report that silencing of the type 1 LPA receptor (LPA(1)) in cancer cells blocks the production of tumor-derived cytokines that are potent activators of osteoclast-mediated bone destruction and significantly reduces the progression of osteolytic bone metastases. Moreover, functional blockade of LPA action on its cognate receptor LPA(1) using a pharmacological antagonist mimics the effects of silencing LPA(1) in tumor cells in vitro and substantially reduces bone metastasis progression in animals. Overall, these results suggest that inhibition of platelet-derived LPA action on LPA, expressed by tumor cells may be a promising therapeutic target for patients with bone metastases.
机译:血小板衍生的溶血磷脂酸(LPA)支持乳腺癌和卵巢癌转移至骨骼的进展。但是,LPA促进骨转移形成的机制尚不清楚。在这里,我们报告说,癌细胞中1型LPA受体(LPA(1))的沉默阻止了肿瘤源性细胞因子的产生,这些细胞因子是破骨细胞介导的骨破坏的有效激活剂,并显着降低了溶骨性骨转移的进程。此外,使用药理拮抗剂对LPA对其同源受体LPA(1)的功能性功能阻断可在体外模拟肿瘤细胞中LPA(1)沉默的作用,并显着降低动物的骨转移进程。总体而言,这些结果表明,抑制肿瘤细胞表达的血小板衍生LPA对LPA的作用可能是骨转移患者的有希望的治疗靶点。

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