Implications of TP-positive CAFs in the Bone Invasion of Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) have recently been suggested as critical cellular components of bone invasion in oral squamous cell carcinoma (OSCC). However, the underlying molecular mechanisms and subtypes related to their bone-invasive function are unclear. This study investigated the implications of thymidine phosphorylase (TP)-positive CAFs (TPCAFs) in OSCC bone invasion.

MATERIALS AND METHODS

TP expression was determined in 116 patients with OSCC using immunohistochemistry. The influence of TP expression on the biological behavior of CAFs was investigated in vitro. The possible impact of TPCAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models.

RESULTS

In bone-invasive OSCC tissues, TPCAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High levels of TPCAFs were significantly associated with higher T-stage, bone invasion, and worse overall survival and recurrence-free survival in our study cohort. Recombinant human TP promoted the proliferative and invasive abilities of CAFs and increased matrix metalloproteinase-9 mRNA expression in vitro, related to bone resorption. In the PDX mouse models, TPCAFs were found in early bone resorption on the surface of resorbed bony tissues. Bone resorption occurred more frequently in the PDX models with TPCAFs than in those without.

CONCLUSION

TPCAFs were significantly associated with bone invasion and the prognosis of OSCC. This study provides insights into cellular and molecular targets for the early diagnosis and treatment of bone-invasive OSCC.