Oral cavity squamous cell carcinoma (OSCC) is the most common oral malignancy, and is increasing in incidence. Bone invasion by OSCC correlates with recurrence and worsened disease-specific survival. OSCC invades adjacent bone by direct extension rather than by metastasis, and previous studies indicated that this invasion is osteoclast-mediated. The mechanisms of bone invasion of OSCC are only partially understood. The purpose of this project is to elucidate osteoactivin's role in OSCC bone invasion. Osteoactivin (OA) was first identified as a gene differentially expressed in melanoma cells with high and low metastatic potentials. OA is known to play a role in invasion, including bone invasion, and metastasis in several malignancies including breast carcinomas, malignant melanoma, and squamous cell lung carcinoma. Moreover, OA promotes osteoclast differentiation and angiogenesis. Our preliminary data indicate that OA is expressed in OSCC cells and promotes tumor cell migration. Tumor-stromal interactions have been shown to promote aggressive behavior in OSCC. We will determine whether OA plays a role in invasion and tumor-induced osteoclast differentiation in OSCC.
In Aim 1 of this project, we will determine if OA promotes OSCC cell migration, and tumor-mediated osteoclastogenesis. Suppression of OA expression in the OSCC cells will be used to confirm OA's effects on tumor invasion, and osteoclast differentiation and activation.
In Aim 2, we will use an animal model of OSCC bone invasion to assess OA's role in osteoclast-mediated tumor bone invasion. This work will expand our understanding of bone invasion by OSCC, and may identify OA is a marker of bone invasion and a potential therapeutic target in OSCC treatment.

Public Health Relevance

Oral cavity cancer is a common disease that is increasing in incidence. Spread to the jaws occurs in one-third of cases of oral cancer, and this spread is associated with significant disfigurement due to surgery and radiation therapy, as well as a worse prognosis for survival. This project investigates how oral cancer spreads to bone by studying the role of a protein called osteoactivin in promoting tumor invasion of normal tissues, and in promoting the differentiation of cells that degrade bone. Osteoactivin will be investigated as a marker of bone invasion by oral cancers, and may prove to be a therapeutic target in this disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA167126-02
Application #
8665396
Study Section
Special Emphasis Panel (ZRG1-OBT-M (55))
Program Officer
Wali, Anil
Project Start
2013-07-01
Project End
2015-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
$164,561
Indirect Cost
$59,073
Name
Temple University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122