Picturing Breast Cancer Brain Metastasis Development to Unravel Molecular Players and Cellular Crosstalk
| العنوان: | Picturing Breast Cancer Brain Metastasis Development to Unravel Molecular Players and Cellular Crosstalk |
|---|---|
| المؤلفون: | János Haskó, Tânia Custódio-Santos, Maria Alexandra Brito, Inês Figueira, Imola Wilhelm, Raquel Vicente, Rui Malhó, Mafalda Videira, Sofia Galego, Kinga Molnár, István A. Krizbai |
| المصدر: | Cancers, Vol 13, Iss 910, p 910 (2021) Cancers Volume 13 Issue 4 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, RHOA, Biology, blood–brain barrier, lcsh:RC254-282, Article, Mural cell, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, medicine, Mesenchymal–epithelial transition, Autocrine signalling, breast cancer brain metastasis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, mesenchymal–epithelial transition, Extravasation, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, intercellular communication, Cancer research, biology.protein, Pericyte, extravasation, microvasculature, Brain metastasis |
| الوصف: | With breast cancer (BC) therapy improvements, the appearance of brain metastases has been increasing, representing a life-threatening condition. Brain metastasis formation involves BC cell (BCC) extravasation across the blood–brain barrier (BBB) and brain colonization by unclear mechanisms. We aimed to disclose the actors involved in BC brain metastasis formation, focusing on BCCs’ phenotype, growth factor expression, and signaling pathway activation, correlating with BBB alterations and intercellular communication. Hippocampi of female mice inoculated with 4T1 BCCs were examined over time by hematoxylin-eosin, immunohistochemistry and immunofluorescence. Well-established metastases were observed at seven days, increasing thereafter. BCCs entering brain parenchyma presented mesenchymal, migratory, and proliferative features however, with time, they increasingly expressed epithelial markers, reflecting a mesenchymal–epithelial transition. BCCs also expressed platelet-derived growth factor-B, β4 integrin, and focal adhesion kinase, suggesting autocrine and/or paracrine regulation with adhesion signaling activation, while balance between Rac1 and RhoA was associated with the motility status. Intercellular communication via gap junctions was clear among BCCs, and between BCCs and endothelial cells. Thrombin accumulation, junctional protein impairment, and vesicular proteins increase reflect BBB alterations related with extravasation. Expression of plasmalemma vesicle-associated protein was increased in BCCs, along with augmented vascularization, whereas pericyte contraction indicated mural cells’ activation. Our results provide further understanding of BC brain metastasis formation, disclosing potential therapeutic targets. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9bb33c0e1e257a250b00ba230172ad3a https://doi.org/10.3390/cancers13040910 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9bb33c0e1e257a250b00ba230172ad3a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
|---|