Intratumoral steroidogenesis is involved in development of castration-resistant prostate cancer (CRPC) as bone metastases. The osteoblast transcription factor RUNX2 influences steroidogenesis and is induced in CRPC cells by osteoblasts. This study investigates osteoclastic influence on RUNX2 in intratumoral steroidogenesis.

Steroidogenic enzymes and steroid receptors were detected with immunohistochemistry in xenograft intratibial tumors from CRPC cells. In vitro, expression of RUNX2 was increased by osteoclasts in osteoblastic LNCaP-19 cells, but not in osteolytic PC-3. Silencing of RUNX2 downregulates expression of CYP11A1, CYP17A1 and HSD3B1 in LNCaP-19 cells co-cultured with osteoclasts, leading to inhibition of KLK3 expression. Osteoclasts promoted CYP11A1 and RUNX2 promoted AKR1C3, HSD17B3 and CYP19A1, but suppressed ESR2 in PC-3 cells.

This study shows that osteoclasts promote RUNX2 regulated induction of key steroidogenic enzymes, influencing activation of androgen receptor in CRPC cells. The potential of RUNX2 as a target to inhibit progression of skeletal metastases of CRPC needs further investigation.

肿瘤内类固醇生成参与作为骨转移的去势抵抗性前列腺癌 (CRPC) 的发展。成骨细胞转录因子 RUNX2 影响类固醇生成，并在 CRPC 细胞中由成骨细胞诱导。本研究调查了肿瘤内类固醇生成中破骨细胞对 RUNX2 的影响。

在来自 CRPC 细胞的异种移植胫骨内肿瘤中，通过免疫组织化学检测了类固醇生成酶和类固醇受体。在体外，破骨细胞在成骨 LNCaP-19 细胞中增加了RUNX2的表达，但在溶骨性 PC-3 中没有。RUNX2的沉默会下调与破骨细胞共培养的 LNCaP-19 细胞中CYP11A1、CYP17A1和HSD3B1的表达，从而导致KLK3表达的抑制。破骨细胞促进CYP11A1和 RUNX2 促进AKR1C3、HSD17B3和CYP19A1，但抑制PC-3 细胞中的ESR2。

该研究表明，破骨细胞促进 RUNX2 调节的关键类固醇生成酶的诱导，影响 CRPC 细胞中雄激素受体的激活。RUNX2 作为抑制 CRPC 骨骼转移进展的靶点的潜力需要进一步研究。