التفاصيل البيبلوغرافية
| العنوان: |
Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution |
| المؤلفون: |
Johannes Robert Fleischer, Alexandra Maria Schmitt, Gwendolyn Haas, Xingbo Xu, Elisabeth Maria Zeisberg, Hanibal Bohnenberger, Stefan Küffer, Laure-Anne Teuwen, Philipp Johannes Karras, Tim Beißbarth, Annalen Bleckmann, Mélanie Planque, Sarah-Maria Fendt, Peter Vermeulen, Michael Ghadimi, Joanna Kalucka, Tiago De Oliveira, Lena-Christin Conradi |
| المصدر: |
Molecular Cancer, Vol 22, Iss 1, Pp 1-22 (2023) |
| بيانات النشر: |
BMC, 2023. |
| سنة النشر: |
2023 |
| المجموعة: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: |
Colorectal cancer liver metastases, Histopathological growth patterns, Vessel co-option, Sprouting angiogenesis, Glycolysis, WNT signalling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: |
Abstract Background Colorectal cancer liver metastases (CRCLM) are associated with a poor prognosis, reflected by a five-year survival rate of 14%. Anti-angiogenic therapy through anti-VEGF antibody administration is one of the limited therapies available. However, only a subgroup of metastases uses sprouting angiogenesis to secure their nutrients and oxygen supply, while others rely on vessel co-option (VCO). The distinct mode of vascularization is reflected by specific histopathological growth patterns (HGPs), which have proven prognostic and predictive significance. Nevertheless, their molecular mechanisms are poorly understood. Methods We evaluated CRCLM from 225 patients regarding their HGP and clinical data. Moreover, we performed spatial (21,804 spots) and single-cell (22,419 cells) RNA sequencing analyses to explore molecular differences in detail, further validated in vitro through immunohistochemical analysis and patient-derived organoid cultures. Results We detected specific metabolic alterations and a signature of WNT signalling activation in metastatic cancer cells related to the VCO phenotype. Importantly, in the corresponding healthy liver of CRCLM displaying sprouting angiogenesis, we identified a predominantly expressed capillary subtype of endothelial cells, which could be further explored as a possible predictor for HGP relying on sprouting angiogenesis. Conclusion These findings may prove to be novel therapeutic targets to the treatment of CRCLM, in special the ones relying on VCO. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1476-4598 |
| Relation: |
https://doaj.org/toc/1476-4598 |
| DOI: |
10.1186/s12943-023-01713-1 |
| URL الوصول: |
https://doaj.org/article/380114cc6bdc4ae19d7ea19ff089eb9c |
| رقم الانضمام: |
edsdoj.380114cc6bdc4ae19d7ea19ff089eb9c |
| قاعدة البيانات: |
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