EGFR inhibition by anti-CD147 therapy in Cutaneous Squamous cell Carcinoma John W Frederick MD1, Larissa Sweeny MD 1, Yolanda Hartman BS1, Tong Zhou2, and Eben L Rosenthal MD1,* From the 1Department of Surgery, Division of Otolaryngology – Head and Neck Surgery, and 2Department of Medicine, Division of Immunology and Rheumatology, University of Alabama at Birmingham, Alabama.
Running Title: CD147 impacts EGFR expression Key Words: Cutaneous squamous cell carcinoma, head and neck, EGFR, CD147, EMMPRIN
Acknowledgements: This work was supported by grants from the AHNS/AAO Pilot Grant and the National Institute of Health (R01 CA142637-01 and 2T32 CA091078-09) No potential conflicts of interest.
________________________ * Corresponding Author: Dr. Eben Rosenthal Division of Otolaryngology Volker Hall G082 1670 University Blvd Birmingham, AL 35233 Tel: (205) 934-9766 Fax: (205) 934-3993 [email protected] Abstract This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/hed.23885
Head & Neck
Page 2 of 19
2
Background: Advanced cutaneous squamous cell carcinoma (cSCC) is an uncommon and aggressive malignancy. As a result, there is limited understanding of its biology and pathogenesis. CD147 and EGFR have been identified as oncologically important targets, but their relationship remains undefined in cSCC Methods: Multiple cSCC cell lines (Colo-16, SRB-1, and SRB-12), were treated in vitro with a range of chimeric anti-CD147 monoclonal antibody (mAb) (0, 50, 100, 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration (scratch wound healing assay), and protein expression was then assessed. In vivo, Colo-16 flank xenografts were treated anti-CD147 mAb (150µg i.p. triweekly). Results: Following treatment with anti-CD147 (200 µg/mL), there was a significant decrease in proliferation for all cell lines relative to control (p
Running Title: CD147 impacts EGFR expression Key Words: Cutaneous squamous cell carcinoma, head and neck, EGFR, CD147, EMMPRIN
Acknowledgements: This work was supported by grants from the AHNS/AAO Pilot Grant and the National Institute of Health (R01 CA142637-01 and 2T32 CA091078-09) No potential conflicts of interest.
________________________ * Corresponding Author: Dr. Eben Rosenthal Division of Otolaryngology Volker Hall G082 1670 University Blvd Birmingham, AL 35233 Tel: (205) 934-9766 Fax: (205) 934-3993 [email protected] Abstract This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/hed.23885
Head & Neck
Page 2 of 19
2
Background: Advanced cutaneous squamous cell carcinoma (cSCC) is an uncommon and aggressive malignancy. As a result, there is limited understanding of its biology and pathogenesis. CD147 and EGFR have been identified as oncologically important targets, but their relationship remains undefined in cSCC Methods: Multiple cSCC cell lines (Colo-16, SRB-1, and SRB-12), were treated in vitro with a range of chimeric anti-CD147 monoclonal antibody (mAb) (0, 50, 100, 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration (scratch wound healing assay), and protein expression was then assessed. In vivo, Colo-16 flank xenografts were treated anti-CD147 mAb (150µg i.p. triweekly). Results: Following treatment with anti-CD147 (200 µg/mL), there was a significant decrease in proliferation for all cell lines relative to control (p
