Extracellular matrix metalloprotease inducer (EMMPRIN or CD147) is a tumor cell surface molecule that is known to promote tumor growth in epithelial malignancies and is highly expressed in head and neck squamous cell carcinoma (HNSCC). We hypothesize that CD147 can be exploited as a therapeutic target in head and neck cancer. We propose to assess the potential of anti-CD147 antibody therapy alone and in combination with concurrent radiation and cisplatin treatment. Furthermore, we propose to determine the role of CD147 in promoting regional metastasis. Although CD147 is known to stimulate fibroblasts to produce matrix metalloproteases (MMPs) and vascular endothelial growth factor (VEGF), we have identified upregulation and secretion of interleukin-12 (IL- 12) in CD147 stimulated fibroblasts. We propose to determine if CD147 promotes the malignant phenotype in vitro and in vivo tumor through modulation of IL-12.

Public Health Relevance

Survival rates for head and neck cancer (HNSCC) have not significantly improved over the past 30 years despite more aggressive treatment and advances in medical treatment. Development of targeted agents against molecules that promote tumor growth have the potential to improve patient outcomes when combined with conventional cytotoxic therapies. We propose to determine if extracellular matrix metalloprotease inducer (EMMPRIN or CD147) is a potential molecular target in HNSCC. The application also seeks to identify the role of CD147 in tumor growth and metastasis using murine orthotopic models of head and neck cancer. Furthermore, novel molecular mechanisms by which CD147 acts to promote the malignant phenotype in vitro and in vivo will be investigated.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Developmental Therapeutics Study Section (DT)
Program Officer
Yovandich, Jason L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Alabama Birmingham
Schools of Medicine
United States
Zip Code
Frederick, John W; Sweeny, Larissa; Hartman, Yolanda et al. (2016) Epidermal growth factor receptor inhibition by anti-CD147 therapy in cutaneous squamous cell carcinoma. Head Neck 38:247-52
Kim, Hyunki; Hartman, Yolanda E; Zhai, Guihua et al. (2015) Dynamic contrast-enhanced MRI evaluates the early response of human head and neck tumor xenografts following anti-EMMPRIN therapy with cisplatin or irradiation. J Magn Reson Imaging 42:936-45
Kim, Hyunki; Rigell, Christopher J; Zhai, Guihua et al. (2014) Antagonistic effects of anti-EMMPRIN antibody when combined with chemotherapy against hypovascular pancreatic cancers. Mol Imaging Biol 16:85-94
Sorace, Anna G; Korb, Melissa; Warram, Jason M et al. (2014) Ultrasound-stimulated drug delivery for treatment of residual disease after incomplete resection of head and neck cancer. Ultrasound Med Biol 40:755-64
Frederick, John W; Sweeny, Larissa; Carroll, William R et al. (2013) Microvascular anastomotic coupler assessment in head and neck reconstruction. Otolaryngol Head Neck Surg 149:67-70
Heath, C Hope; Deep, Nicholas L; Beck, Lauren N et al. (2013) Use of panitumumab-IRDye800 to image cutaneous head and neck cancer in mice. Otolaryngol Head Neck Surg 148:982-90
Kejner, Alexandra E; Burch, M Benjamin; Sweeny, Larissa et al. (2013) Bone morphogenetic protein 6 expression in oral cavity squamous cell cancer is associated with bone invasion. Laryngoscope 123:3061-5
Day, Kristine E; Sweeny, Larissa; Kulbersh, Brian et al. (2013) Preclinical comparison of near-infrared-labeled cetuximab and panitumumab for optical imaging of head and neck squamous cell carcinoma. Mol Imaging Biol 15:722-9
Heath, C Hope; Deep, Nicholas L; Nabell, Lisle et al. (2013) Phase 1 study of erlotinib plus radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Int J Radiat Oncol Biol Phys 85:1275-81
Day, Kristine E; Beck, Lauren N; Deep, Nicholas L et al. (2013) Fluorescently labeled therapeutic antibodies for detection of microscopic melanoma. Laryngoscope 123:2681-9

Showing the most recent 10 out of 45 publications