Fibroblast-associated protection against hypoxia and carboplatin-induced cytotoxicity during coculture with...

Osteosarcoma progression and treatment resistance are strongly influenced by the tumour microenvironment. One of the key players in tumour microenvironments is cancer-associated fibroblast. Much of the conventional cancer-associated fibroblast-centred research paradigm focuses on the secretory and matrix-remodelling aspects of fibroblasts. However, less is known on how fibroblasts influence osteosarcoma cell behaviour, particular under stress.

In a proof-of-concept study, human dermal fibroblasts and osteosarcoma cells were studied using direct coculture and size-restricted transwell systems. Fluorescent labelling, confocal microscopy, live-cell imaging, and single-cell tracking were used to assess intercellular transfer, migratory behaviour, proliferation, and survival under chemotherapy and hypoxic challenge.

Osteosarcoma cells acquired fibroblast-derived, mitochondria cargo-enriched material in both direct and indirect coculture systems, with transfer of material enhanced under carboplatin and hypoxic stress. Notably, fibroblast coculture increased osteosarcoma cell migration and promoted survival under stress but did not substantially increase basal proliferation.

These findings suggest that fibroblast-to-cancer cell transfer of mitochondria-enriched cargo is accelerated during stress conditions with the concomitant observation of proportional osteosarcoma protection to degree of fibroblast cargo transfer. Further research should examine stress-amplified transfer during tumour adaptation, chemoresistance, and metastatic behaviour, potentially highlighting stromal intercellular communication as an important aspect of osteosarcoma biology.