Dissection and destruction of bone metastasis facilitated by new models
Whereas most overt bone metastases in breast cancer are osteolytic, our previous studies demonstrated that breast cancer bone micrometastases exhibit an osteoblast-dependent behavior prior to initiation of osteolysis.
Our central hypothesis is that breast micrometastasis and the indolent bone progression of osteoblastic prostate cancer share commonalities, supporting application of our knowledge and expertise (e.g., intra-iliac artery [IIA] injection and bone-in-culture array [BICA] analysis) to understanding prostate cancer bone metastasis.
Technically, BICA is based on IIA injection, which is performed by selectively delivering cancer cells into the hind limbs of mice via the external iliac artery; followed by extracting and fragmenting the cancer-containing bones, and exposing the bone fragments to ex vivo cultures. As a faithful model for early-stage bone colonization, BICA mimics the slow kinetics of prostate cancer cells.
In our following effort, we will further improve BICA by reducing the variation and increasing the capacity of this platform, apply this platform to investigate the interaction between the bone microenvironment and prostate cancer, and perform high-throughput screening (HTS) for prostate cancer bone metastasis-specific drugs.
Combined with the knowledge gained from previous studies, the fulfillment of our research objectives will ultimately provide insight into the organotrophic progression of bone metastasis and offer guidance for development of the urgently needed therapeutic strategies to cure skeletal lesions.
Optimization and Characterization of a Bone Culture Model to Study Prostate Cancer Bone Metastasis
- Journal: Molecular Cancer Therapy, August 2022
- Authors: Wu YH, Gugala Z, Barry MM, Shen Y, Dasgupta S, Wang H.
- Citation: Mol Cancer Ther. 2022 Aug 2;21(8):1360-1368. doi: 10.1158/1535-7163.MCT-21-0684