Exogenous expression of caspase-14 induces tumor suppression in human salivary cancer cells by inhibiting tumor vascularization.

BACKGROUND Current therapeutic approaches to salivary gland cancer are often associated with severe disfigurement and loss of glandular function, which are traumatic to the patients. Exploration of novel treatment approaches, such as gene therapy, is needed. MATERIALS AND METHODS The human salivary gland cancer cell line HSG was transiently transfected with full length human caspase-14 cDNA. Photomicroscopy, BrdU assay, cell counting, MTT assay, and TUNEL assay were applied. To determine the tumorigenicity, tumor volume, tumor pathology and vascularization were analyzed in vivo. RESULTS Cell growth and viability were inhibited significantly by transient caspase-14 expression. Caspase-14 expression resulted in a significant reduction of tumorigenicity. Importantly, a significant decrease in tumor blood vessel formation was observed. CONCLUSION Salivary gland cancer cells underwent growth inhibition, cell death, and reduced tumorigenicity in vivo when exogenous caspase-14 was expressed, which could be due, in part, to an inhibitory effect of caspase-14 on tumor vascularization.

[1]  L. Eckhart,et al.  Caspase-14: analysis of gene structure and mRNA expression during keratinocyte differentiation. , 2000, Biochemical and biophysical research communications.

[2]  S. Kyakumoto,et al.  [Proliferation and differentiation of human salivary gland adenocarcinoma cell line HSG]. , 1996, Human cell.

[3]  M. Duffy,et al.  Tumor-Associated Alterations in Caspase-14 Expression in Epithelial Malignancies , 2005, Clinical Cancer Research.

[4]  D. Dickinson,et al.  Expression of caspase-14 reduces tumorigenicity of skin cancer cells. , 2007, In vivo.

[5]  V. Devita,et al.  Cancer : Principles and Practice of Oncology , 1982 .

[6]  K. Madison,et al.  Barrier function of the skin: "la raison d'être" of the epidermis. , 2003, The Journal of investigative dermatology.

[7]  D. Dickinson,et al.  Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren's syndrome, an autoimmune disease. , 2008, Life sciences.

[8]  B. Nickoloff,et al.  Life and death signaling pathways contributing to skin cancer. , 2002, The journal of investigative dermatology. Symposium proceedings.

[9]  Maccomb Ws.  Treatment of head and neck cancer. , 1960 .

[10]  D. Dickinson,et al.  Protective effects of EGCG on salivary gland cells treated with gamma-radiation or cis-platinum(II)diammine dichloride. , 2004, Anticancer research.

[11]  P. Vandenabeele,et al.  Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing , 2000, Cell Death and Differentiation.

[12]  P. Vandenabeele,et al.  Caspase-14 protects against epidermal UVB photodamage and water loss , 2007, Nature Cell Biology.

[13]  Nam Jin Yoo,et al.  Mutational analysis of caspase‐14 gene in common carcinomas , 2007, Pathology.

[14]  W. Bollag,et al.  Green tea polyphenols reduce autoimmune symptoms in a murine model for human Sjogren's syndrome and protect human salivary acinar cells from TNF-α-induced cytotoxicity , 2007 .

[15]  M. Kan,et al.  Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Jean-Claude Vatin,et al.  La raison d'être , 1992 .

[17]  L. Eckhart,et al.  Caspase-14 expression by epidermal keratinocytes is regulated by retinoids in a differentiation-associated manner. , 2002, The Journal of investigative dermatology.

[18]  B. O'Malley,et al.  Combination Gene Therapy for Salivary Gland Cancer , 1998, Annals of the New York Academy of Sciences.

[19]  P. Speight,et al.  Salivary gland tumours. , 2002, Oral diseases.

[20]  P. Bradley,et al.  Diagnosis and Classification of Salivary Neoplasms: Pathologic Challenges and Relevance to Clinical Outcomes , 2002, Acta oto-laryngologica.