Expression and Roles of S100A4 in Anaplastic Cells of Canine Mammary Carcinomas
| Autor: | Shinji Kamiya, Masaki Michishita, Hisashi Yoshimura, Minori Ashizawa, Daigo Azakami, Aya Otsuka, Toshiyuki Ishiwata, Masami Yamamoto, Yoko Matsuda, Kazuhiko Ochiai, Maiko Moriya, Manami Zushi, Kimimasa Takahashi |
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| Rok vydání: | 2019 |
| Předmět: |
Canine Mammary Carcinoma
Small interfering RNA Stromal cell General Veterinary Cell growth Carcinoma Mammary Neoplasms Animal Cell migration Transfection Biology Real-Time Polymerase Chain Reaction Dogs Mammary Glands Animal Immunophenotyping Cell culture Cell Line Tumor Cancer research Animals Female S100 Calcium-Binding Protein A4 Dog Diseases |
| Zdroj: | Veterinary Pathology. 56:389-398 |
| ISSN: | 1544-2217 0300-9858 |
| Popis: | S100A4 (metastasin), a member of the S100 protein family, was initially identified in metastatic cells and is well established as a marker of aggressive human cancer. However, expression and roles of S100A4 in canine mammary tumors have not been clarified. In this study, expression of S100A4 was examined immunohistochemically in normal, hyperplastic, and neoplastic mammary glands of dogs. In all normal and benign lesions, S100A4 was restricted to a few stromal fibroblasts and inflammatory cells. However, in 7 of 57 (12%) of the malignant tumors examined, cytoplasmic and nuclear expression of S100A4 was observed in epithelial tumor cells and stromal cells. Particularly, the frequency of S100A4-positive anaplastic carcinomas was high (4/8 cases, 50%). Next, we established a novel cell line, named NV-CML, from a S100A4-positive canine mammary carcinoma. The cultured NV-CML cells and the tumors that developed in the immunodeficient mice after subcutaneous injection of the cells maintained the immunophenotype of the original tumor, including S100A4 expression. Using this cell line, we examined the cellular functions of S100A4 using RNA interference. S100A4 expression level in NV-CML cells transfected with small interfering RNA (siRNA) targeting canine S100A4 (siS100A4) was reduced to about one-fifth of those with negative-control siRNA (siNeg). Cell proliferation in WST-8 assay and cell migration in Boyden chamber assay were significantly decreased in siS100A4-transfected cells compared with siNeg-transfected cells. These findings suggest that S100A4 may be related to progression of canine mammary carcinomas via its influence on cell growth and motility. |
| Databáze: | OpenAIRE |
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