Young Sun Hwang1, Sung Yong Ahn2, Sook Moon3, Zhenlong Zheng4, In-Ho Cha5, Jin Kim2, Xianglan Zhang6. 1. Department of Dental Hygiene, College of Health Science, Eulji University, Seoul, Korea. 2. Department of Oral Pathology, Graduate School, Yonsei University College of Dentistry, Seoul, Korea; Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea. 3. Department of Oral Pathology, Graduate School, Yonsei University College of Dentistry, Seoul, Korea. 4. Department of Dermatology, Yanbian University Hospital, Yanji City, Jilin province, China. 5. Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea. 6. Department of Pathology, Yanbian University Hospital, Yanji City, Jilin province, China; Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea. Electronic address: zhangxianglan@yuhs.ac.
Abstract
OBJECTIVE: This study aimed to evaluate the prognostic implications of insulin-like growth factor-II mRNA binding protein-3 (IMP3) and podoplanin (PDPN) as therapeutic targets against oral squamous cell carcinoma (OSCC) with bone invasion. STUDY DESIGN: We elucidated the correlation of IMP3 and PDPN expression with bone invasion in 160 OSCC tissue specimens, and assessed a mouse calvarium xenograft model using an IMP3- and PDPN-depleted OSCC cell line. RESULTS: The retrospective analysis revealed that the expression of IMP3 and PDPN is significantly correlated with T stage, lymph node metastasis, and the overall survival of OSCC patients. In addition, the dual expression of IMP3 and PDPN but not the single expression of either IMP3 or PDPN was associated with bone invasion and the number of osteoclasts in patients with OSCC. In support of these findings, IMP3 or PDPN depletion inhibited the invasive capacity of OSCC cells in a three-dimensional culture system, tumorigenesis, and regional bone destruction in a xenograft mouse model. In addition, IMP3 or PDPN depletion inhibited the expression of interleukin (IL)-6 and IL-8 in OSCC cells, and decreased the expression of receptor activator of NF-κB ligand (RANKL) in xenograft tumor tissues of OSCC. CONCLUSIONS: These results suggest that IMP3 and PDPN may have strong influence on the pathogenesis of OSCC, especially in bone invasion, and may serve as novel therapeutic targets with prognostic implications for bone-invasive OSCC.
OBJECTIVE: This study aimed to evaluate the prognostic implications of insulin-like growth factor-II mRNA binding protein-3 (IMP3) and podoplanin (PDPN) as therapeutic targets against oral squamous cell carcinoma (OSCC) with bone invasion. STUDY DESIGN: We elucidated the correlation of IMP3 and PDPN expression with bone invasion in 160 OSCC tissue specimens, and assessed a mouse calvarium xenograft model using an IMP3- and PDPN-depleted OSCC cell line. RESULTS: The retrospective analysis revealed that the expression of IMP3 and PDPN is significantly correlated with T stage, lymph node metastasis, and the overall survival of OSCC patients. In addition, the dual expression of IMP3 and PDPN but not the single expression of either IMP3 or PDPN was associated with bone invasion and the number of osteoclasts in patients with OSCC. In support of these findings, IMP3 or PDPN depletion inhibited the invasive capacity of OSCC cells in a three-dimensional culture system, tumorigenesis, and regional bone destruction in a xenograft mouse model. In addition, IMP3 or PDPN depletion inhibited the expression of interleukin (IL)-6 and IL-8 in OSCC cells, and decreased the expression of receptor activator of NF-κB ligand (RANKL) in xenograft tumor tissues of OSCC. CONCLUSIONS: These results suggest that IMP3 and PDPN may have strong influence on the pathogenesis of OSCC, especially in bone invasion, and may serve as novel therapeutic targets with prognostic implications for bone-invasive OSCC.
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