Develevopment of a New Therapeutic Avenue for Basal Cell Carcinoma Eyelid Tumors

Purpose: Basal Cell Carcinoma (BCC) is the most common periocular malignancy. BCC is usually managed surgically, with subsequent aesthetic and functional implications. Recently, innovative treatment with smoothened inhibitors was thoroughly investigated, but substantial side-effects limit its use. As the search for cure continues, the common available BCC models, conducted by UV or ionizing radiation (IR) in knocked out mice, pose their own limitations. Our study aims to generate a novel model system of eyelid BCC in mice, through which to investigate the tumor`s microenvironment and to suggest novel treatments for BCC tumors.

Methods: Murine BCC cells were injected into the eyelids of C57black mice, followed by injection of PBS solution, bevasizumab, or anti- platelet-derived growth factor (PDGF). The mice were monitored for tumor growth and sacrificed. The tumors underwent pathological and histological examinations. The cells secretion of matrix metalloproteinases (MMPs) was investigated by zymography assay.

Results: Murine BCC cells were injected into the eyelids of C57black mice. The mice were then randomly divided into three groups; control and treated with either bevasizumab or anti-PDGF. Tumors were seen in 90%, 80% and 44% of the PBS, anti-PDGF and bevasizumab treated mice, respectively. Bevasizumab decreased the rate of tumor progression compared to anti-PDGF and control groups. In the zymography assay tumor necrosis factor-α (TNFα) demonstrated increase in the secretion of MMP-2.

Conclusions: Murine BCC model can be generated by direct injection of tumor cells. Development of BCC is abrogated by direct bevasizumab injection. In contrast, the use of anti-PDGF does not affect tumor initiation and progression. Tumor invasiveness is suggested to be related to MMP-2 secretion. The results may indicate bevasizumab as adjuvant treatment for BCC tumors.