Lester and Sue Smith Breast Center, Baylor College of Medicine, One Baylor Plaza, Houston, Taxes.
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Taxes.
Mol Cancer Ther. 2022 Aug 2;21(8):1360-1368. doi: 10.1158/1535-7163.MCT-21-0684.
Nearly 90% of patients with advanced prostate cancer manifest bone metastases. Distinct from the osteolytic metastasis mostly observed in other cancer types, prostate cancer bone metastasis is typically more osteoblastic, which is relatively understudied due to the lack of reliable and efficient models to resemble the indolent cellular growth and complexity of metastatic progression. In our previous studies, we developed bone-in-culture array (BICA) to primarily model the osteoblast-involved, pre-osteolytic stage of breast cancer bone metastasis. Given that the progression of prostate cancer bone metastasis is largely osteoblastic, it is reasonable to speculate that the original BICA model can be adjusted to investigate prostate cancer bone metastases. In this study, we refined BICA by reducing the surgical labor and improving its reproducibility and capacity. The optimized BICA can successfully recapitulate important features of prostate cancer bone metastasis such as the osteoblastic phenotype, indolent growth, cancer-niche interactions, and response to hormones. Our efforts address the long-standing need for reliable and efficient models to study prostate cancer bone metastasis.
近 90%的晚期前列腺癌患者有骨转移。与其他癌症类型中观察到的溶骨性转移不同,前列腺癌骨转移通常更成骨,由于缺乏可靠和有效的模型来模拟惰性细胞生长和转移进展的复杂性,因此相对研究较少。在我们之前的研究中,我们开发了骨培养阵列(BICA),主要用于模拟乳腺癌骨转移中涉及成骨细胞的、前溶骨性阶段。鉴于前列腺癌骨转移的进展在很大程度上是成骨的,因此可以合理地推测,原始 BICA 模型可以进行调整以研究前列腺癌骨转移。在这项研究中,我们通过减少手术工作量和提高其可重复性和容量来改进 BICA。优化后的 BICA 可以成功重现前列腺癌骨转移的重要特征,如成骨表型、惰性生长、癌症-生态位相互作用以及对激素的反应。我们的努力满足了研究前列腺癌骨转移的可靠和高效模型的长期需求。