Bone metastasis occurs in approximately 85% of patients with advanced prostate cancer (PCa) and is the primary cause of PCa-related mortality. Recently, a research team led by Chief Physician Mao Yilei and Researcher Yang Huayu from Peking Union Medical College Hospital (PUMCH) published a groundbreaking study in the Journal of Advanced Research (IF=17.1). The team utilized 3D bioprinting technology to engineer a biomimetic osteogenic niche co-culture model that recapitulates the PCa bone-metastatic microenvironment. This platform deciphers how the bone microenvironment drives malignant progression and therapeutic resistance, establishing a novel in vitro system for preclinical drug screening.

Historically, research on PCa bone metastasis has been hindered by limitations in experimental modeling, posing major bottlenecks for investigating drug resistance mechanisms and evaluating new drugs. Conventional 2D monolayer cultures fail to recapitulate native 3D tissue architecture; organoid cultures exhibit substantial batch-to-batch variability; and patient-derived xenograft (PDX) models remain cost-prohibitive with prolonged experimental timelines. 3D bioprinting addresses these challenges by precisely positioning cells and biomaterials to reliably reconstruct complex, multicellular microenvironments with high structural stability and reproducibility.

In this study, the researchers utilized gelatin methacryloyl (GelMA) as the primary bioink to construct 3D-PCa tumor models and osteogenic differentiation models derived from adipose-derived stem cells (ADSCs). The 3D-bioprinted constructs maintained sustained cell viability and structural stability over extended culture. To capture different progression stages of the disease, the team incorporated both LNCaP and PC-3 cells, modeling androgen-dependent and castration-resistant prostate cancer, respectively.

Compared to 2D cultures, PCa cells within the 3D-bioprinted models exhibited enhanced invasive potential, marked resistance to chemotherapeutic agents and PARP inhibitors, and heightened adaptation to androgen-deprivation. When the 3D-PCa models were co-cultured with pre-differentiated 3D osteogenic constructs, the team observed a pivotal phenomenon: the osteogenic niche further amplified malignant phenotypes—promoting cancer cell proliferation, invasion and migration while diminishing sensitivity to multiple anti-cancer therapeutics. Crucially, these malignant alterations persisted even when PCa cells and osteogenic cells were physically separated without direct contact, demonstrating that the osteogenic niche drives tumor aggressiveness predominantly via paracrine signaling.

Researcher Yang Huayu noted that this 3D-bioprinted co-culture platform faithfully recapitulates key biological hallmarks of the PCa bone-metastatic microenvironment. It can elucidate the molecular mechanisms by which the bone microenvironment regulates tumor progression, while providing an efficient and accessible in vitro platform for novel drug discovery and personalized treatment evaluation in bone-metastatic prostate cancer. Moving forward, the team plans to integrate patient-derived primary tumor cells, incorporate diverse stromal and immune cell populations, and leverage microfluidic technologies to further elevate the model's translational and clinical value.

Written by Gan Dingzhu

Edited by Gan Dingzhu and Shi Zhenzhen

Chief editor Duan Wenli

Supervised by Wu Peixin