Nintedanib treatment delays prostate dorsolateral lobe cancer progression in the TRAMP model: contribution to the epithelial-stromal interaction balance
| Autor: | Fabio Montico, Ellen Nogueira Pangrazi, Valéria Helena Alves Cagnon, Raquel Frenedoso da Silva, Larissa Akemi Kido |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Angiogenesis Cancer Cell Biology General Medicine Biology medicine.disease Fibroblast growth factor 03 medical and health sciences Prostate cancer chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure chemistry Prostate 030220 oncology & carcinogenesis Immunology medicine Cancer research Adenocarcinoma Nintedanib Tramp |
| Zdroj: | Cell Biology International. 42:153-168 |
| ISSN: | 1065-6995 |
| DOI: | 10.1002/cbin.10881 |
| Popis: | Prostate cancer (PCa) progression mechanism has been linked to epithelial proliferation, tumor invasion ability, and growth factors. Nintedanib (BIBF 1120) has been reported as being FGF and VEGF pathway inhibitors, exhibiting antitumor activity. Thus, the objective herein was to characterize the early Nintedanib treatment effects on the structure and molecules involved in the basal membrane, the extracellular matrix (ECM) maintenance, in addition to the angiogenesis and mitogenic processes at different grades of prostatic tumor development in TRAMP mice. Therefore, 45 male TRAMP mice were divided into control groups: 8-week-old mice (TC8), 12-week-old mice (TC12), and 16-week-old mice (TC16); and treated groups with 10 mg/kg/day Nintedanib dose for 4 weeks. The treated groups were euthanized at 12 (TN12) and 16 (TN16) weeks of age. Samples from the dorsolateral lobe were collected and processed for light microscopy, immunohistochemistry, Western blotting, and microvessel density analysis. The results showed that early Nintedanib treatment led to an increase of healthy epithelium frequency and a reduction of LGPIN and a maximum vascularization density in the TN12 group. Also, treatment led to a well-differentiated adenocarcinoma decrease and an α and β dystroglycan and also laminin 1 increase in the TN16 group. IGFR1 decreased in the TN16 group. To conclude, early Nintedanib treatment led to a reduction in cancer severity, interfering in both ECM compounds and angiogenesis process to then contribute to a balance, not only in the prostatic epithelium and stroma, but also in the epithelial-stromal interaction during PCa progression. |
| Databáze: | OpenAIRE |
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