Dr Randall on the Applicability of Bioengineered Bone Marrow Models for Metastasis Control in Sarcoma

"This is a theoretical discussion [based on] a technical paper, but hopefully, it will incite thoughts of ways by which we can approach cancer [management], not just to try to cure patients, but to push [disease] into a chronic state."

R. Lor Randall, MD, FACS, the David Linn Endowed Chair for Orthopedic Surgery, chair of the Department of Orthopedic Surgery, and a professor at the University of California, Davis, discussed next steps for investigating the applicability of 3-dimensional models of the sarcoma tumor microenvironment (TME) for studying disease behavior in sarcoma subtypes beyond osteosarcoma.

A 2025 study published in Biomaterials Advances by Randall and colleagues evaluated osteosarcoma behavior using a bioengineered bone marrow matrix designed to closely resemble the native tumor niche of osteosarcoma. Findings demonstrated that osteosarcoma exhibits heightened sensitivity to oxygen tension when cultured in a 3-dimensional setting, a property not as clearly observed in traditional 2-dimensional cultures. Moreover, interactions between osteosarcoma cells and macrophages were found to vary depending on the tumors’ metastatic potential, suggesting a possible link between immune cell engagement and disease aggressiveness.

These insights have prompted further interest in whether similar modeling could be extended to the study of other sarcoma subtypes, such as pleomorphic soft tissue sarcomas, Randall stated. Many of these malignancies lack defined oncogenic translocations or singular molecular drivers, presenting a significant challenge in therapeutic targeting and disease modeling, he explained. Investigators have proposed applying the same tissue-mimetic approach to better understand how the TME influences metastatic behavior in these genetically complex sarcomas, he shared.

By embedding tumor cells into a connective tissue matrix that mimics their native stromal environment, researchers aim to assess whether metastatic and nonmetastatic phenotypes can be distinguished and manipulated in vitro, Randall detailed. The long-term goal is to explore whether metastatic traits can be reverted or suppressed, shifting the disease trajectory from aggressive and disseminated to indolent or locally confined, he said. Although these efforts remain in theoretical and preclinical stages, they highlight a potential paradigm shift in sarcoma management—moving beyond curative strategies toward disease modulation and chronic disease control, Randall concluded.