RT Journal Article
SR Electronic
T1 Implications of TP-positive CAFs in the Bone Invasion of Oral Squamous Cell Carcinoma
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3365
OP 3374
DO 10.21873/anticanres.17157
VO 44
IS 8
A1 GAO, AIHUA
A1 KIM, DONG WOOK
A1 PEI, MEILING
A1 KIM, KI-YEOL
A1 PARK, YOUNG-JIN
A1 NAM, WOONG
A1 KIM, HYUNG JUN
A1 KIM, HYUN SIL
A1 CHA, IN-HO
A1 ZHANG, XIANGLAN
YR 2024
UL http://ar.iiarjournals.org/content/44/8/3365.abstract
AB 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 (TP+CAFs) 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 TP+CAFs on bone invasion in OSCC was further evaluated using patient-derived xenograft (PDX) mouse models. Results: In bone-invasive OSCC tissues, TP+CAFs were mainly distributed on the surface of resorbed bone tissue rather than on the tumor side. High levels of TP+CAFs 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, TP+CAFs were found in early bone resorption on the surface of resorbed bony tissues. Bone resorption occurred more frequently in the PDX models with TP+CAFs than in those without. Conclusion: TP+CAFs 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.