Tumor-targeting adenovirus OBP-401 inhibits primary and metastatic tumor growth of triple-negative breast cancer in orthotopic nude-mouse models
| Autor: | Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara, Michael Bouvet, Robert M. Hoffman, Shunsuke Kagawa, Kiyoto Takehara, Shuya Yano, Hiroyuki Kishimoto |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Mammary gland Mice Nude Triple Negative Breast Neoplasms medicine.disease_cause Metastasis Adenoviridae 03 medical and health sciences Mice 0302 clinical medicine Breast cancer Nude mouse Mammary Glands Animal Cell Line Tumor medicine Animals Humans Neoplasm Metastasis Telomerase Oncolytic Virotherapy variants biology business.industry OBP-401 adenovirus medicine.disease biology.organism_classification Primary tumor Xenograft Model Antitumor Assays high-metastatic 3. Good health Disease Models Animal 030104 developmental biology medicine.anatomical_structure Lymphatic system Oncology Organ Specificity 030220 oncology & carcinogenesis triple-negative breast cancer Female Lymph business TNBC nude mouse Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Our laboratory previously developed a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of the human MDA-MB-231 cell line in nude mice. The isolated variant was highly-invasive in the mammary gland and lymphatic channels and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present study, the tumor-selective telomerase dependent OBP-401 adenovirus was injected intratumorally (i.t.) (1 × 108 PFU) when the high-metastatic MDA-MB-231 primary tumor expressing red fluorescent protein (MDA-MB-231-RFP) reached approximately 500 mm3 (diameter; 10 mm). The mock-infected orthotopic primary tumor grew rapidly. After i.t. OBP-401 injection, the growth of the orthotopic tumors was arrested. Six weeks after implantation, the fluorescent area and fluorescence intensity showed no increase from the beginning of treatment. OBP-401 was then injected into high-metastatic MDA-MB-231-RFP primary orthotopic tumor growing in mice which already had developed metastasis within lymphatic ducts. All 7 of 7 control mice subsequently developed lymph node metastasis. In contrast, none of 7 mice which received OBP-401 had lymph node metastasis. Seven of 7 control mice also had gross lung metastasis. In contrast, none of the 7 mice which received OBP-401 had gross lung metastasis. Confocal laser microscopy imaging demonstrated that all control mice had diffuse lung metastases. In contrast, all 7 mice which received OBP-401 only had a few metastatic cells in the lung. OBP-401 treatment significantly extended survival of the treated mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|