Abstract 10P
Background
Breast cancer (BC) was shown to relapse faster and displayed therapeutic resistance to antiangiogenic therapies (AATs) through an alternative tumor cell-driven mechanism of neovascularization called vascular mimicry (VM). This study aims to ascertain the correlation between Angiomotin-p130 expressing and the formation of VM in antiangiogenic therapy.
Methods
Human BC tissue sections and tissue array were used to ascertain the clinical relevance of Angiomotin-p130 expressing in tumor cells and the formation of VM. We utilized MCF7 and MD-MBA-231 human tumor cells to observe VM in an orthotopic BC model and bevacizumab (anti-VEGF) was used to identify the resistance mechanism of antiangiogenic therapies in breast cancer. Later, tube formation assay was used to explore the efficacy of bevacizumab and anlotinib (anti-VEGFR,PDGFR,FGFR and c-Kit) in the inhibition of VM.
Results
According to human datasets and histological analysis Angiomotin-p130 was identified as a bonafide candidate to regulation VM formation through in vitro and in vivo experiments. Stable overexpression of Angiomotin-p130 in tumor cells led to decreased tumor growth as well as incomplete VM structures in the animal models. We identified highly downregulated Angiomotin-p130 in human breast tumor cells and AAT-treated orthotopic mammary tumors. AAT-treated (bevacizumab and anlotinib) tumors displayed a higher number of Angiomotin-p130-negative tumor cells than endothelial-like phenotypes. Tube formation assay showed that the bevacizumab and anlotinib had no significant difference in inhibition on VM, though anlotinib inhibited the proliferation of tumor cells.
Conclusions
The present study suggests that tumor cell autonomous Angiomotin-p130 pathway may play an important role in AAT-mediated resistance and VM formation in BC. Therefore, targeting Angiomotin-p130 can be combined with standard antiangiogenic therapies to improve the therapeutic outcomes in clinical trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Yanwei Shen.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.