Bone-adapted oral squamous cell carcinoma cells show adaptive responses to the osseous microenvironment in a murine tumor transplantation model

Abstract Bone invasion is a decisive step in the progression of oral squamous cell carcinoma (OSCC) and is associated with increased tumor aggressiveness, worsening the prognosis. Under the selection pressure of the bone microenvironment, a fundamental biological divergence arises. Bone-adapted cells represent not only a variant but also a distinct subpopulation with stable pro-invasive properties. To model tumor biological selection through the bone microenvironment, the murine OSCC cell line SCC-7 was injected under the periosteum of immunocompetent C3H mice and cultured in situ for a period of 25 days. A cell population was then isolated from the induced bone-invasive tumor and established in vitro. The selected cells were systematically characterized. Migration and invasion behavior, cellular morphology, size, and metabolism were examined using standardized functional and metabolic analysis methods. Compared with the parental tumor cell line, bone-selected SCC-7 cells showed significantly increased migration and invasion activity as well as clear morphological differences. A constant change in the metabolic profile was detected. Phenotypic alterations indicated adaptive reprogramming as a result of exposure to the bone microenvironment, which selects for a distinct, stably altered tumor cell population. Thus, bone-infiltrating OSCC cells fundamentally differ phenotypically and metabolically from non-bone-invasive tumor cells.