Hypoxia Triggers the Intravasation of Clustered Circulating Tumor Cells
| العنوان: | Hypoxia Triggers the Intravasation of Clustered Circulating Tumor Cells |
|---|---|
| المؤلفون: | Walter P. Weber, Aino Paasinen-Sohns, Cinzia Donato, Nunzia Di Maggio, Marcus Vetter, Nicola Aceto, Oliver Biehlmaier, Karin Strittmatter, Leo Kunz, Timm Schroeder, Wolf Heusermann, Christoph Rochlitz, Christian Beisel, Barbara Maria Szczerba, Ramona Scherrer, Andrea Banfi, Francesc Castro-Giner |
| المصدر: | Cell Reports Cell Reports, 32 (10) |
| بيانات النشر: | Cell Press, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Proteomics, education, General Biochemistry, Genetics and Molecular Biology, Article, Metastasis, Lesion, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Circulating tumor cell, medicine, Animals, Humans, Intravasation, Hypoxia (medical), medicine.disease, Neoplastic Cells, Circulating, Primary tumor, Cell Hypoxia, 3. Good health, Vascular endothelial growth factor, 030104 developmental biology, chemistry, Cancer research, Female, Breast cancer cells, medicine.symptom, 030217 neurology & neurosurgery |
| الوصف: | Summary Circulating tumor cells (CTCs) are shed from solid cancers in the form of single or clustered cells, and the latter display an extraordinary ability to initiate metastasis. Yet, the biological phenomena that trigger the shedding of CTC clusters from a primary cancerous lesion are poorly understood. Here, when dynamically labeling breast cancer cells along cancer progression, we observe that the majority of CTC clusters are undergoing hypoxia, while single CTCs are largely normoxic. Strikingly, we find that vascular endothelial growth factor (VEGF) targeting leads to primary tumor shrinkage, but it increases intra-tumor hypoxia, resulting in a higher CTC cluster shedding rate and metastasis formation. Conversely, pro-angiogenic treatment increases primary tumor size, yet it dramatically suppresses the formation of CTC clusters and metastasis. Thus, intra-tumor hypoxia leads to the formation of clustered CTCs with high metastatic ability, and a pro-angiogenic therapy suppresses metastasis formation through prevention of CTC cluster generation. Graphical Abstract Highlights • Hypoxia leads to cell-cell junction upregulation and intravasation of CTC clusters • Hypoxic CTC clusters are highly metastatic compared to normoxic CTCs • Increase in intra-tumor hypoxia leads to accelerated metastasis • Treatment with EpB2 reduces hypoxia and prevents CTC cluster formation Donato et al. show that intra-tumor hypoxia leads to cell-cell junction upregulation and formation of hypoxic CTC clusters with high metastatic ability. Treatment with EphrinB2 improves tumor vascularization and decreases hypoxia, leading to a reduced CTC cluster shedding rate and suppression of metastasis. |
| وصف الملف: | application/pdf; application/application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b29f6aa8868d49b485c6d1f9ae3e326 https://edoc.unibas.ch/78597/ |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4b29f6aa8868d49b485c6d1f9ae3e326 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |