Vasculogenic mimicry is associated with trastuzumab resistance of HER2-positive breast cancer

Breast Cancer Research : BCR
Ami HoriShinzaburo Noguchi

Abstract

Trastuzumab is a drug that targets the receptor tyrosine kinase HER2 and is essential for the treatment of HER2-positive breast cancer. Resistance to the drug leads to severe consequences, including disease recurrence, tumor enlargement, and metastasis. We hypothesized that trastuzumab treatment might be associated with phenotypic switching in HER2-positive breast cancer cells (BCCs), enabling them to escape and survive the effect of trastuzumab. We conducted comprehensive immunophenotyping to detect phenotypic changes in HER2-positive BCCs treated with trastuzumab, based on criteria determined a priori. Based on immunophenotyping results, we characterized the vascular phenotypes of HER2-positive BCCs by western blotting, real-time RT-PCR, and tube formation assay. The vascular phenotype of tumor cells from clinical samples was evaluated by staining with periodic acid-Schiff and an anti-CD31 antibody. We explored small molecule inhibitors that suppress tube formation and determined the inhibitory mechanism. Out of 242 cell surface antigens, 9 antigens were significantly upregulated and 3 were significantly downregulated by trastuzumab treatment. All upregulated antigens were related to endothelial and stem cell phenotypes, sugg...Continue Reading

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Citations

Jan 11, 2020·Frontiers in Oncology·Maria Carolina Mangini PradoCarlos Eduardo Fonseca-Alves
Mar 15, 2020·Journal of Hematology & Oncology·Qingxi LuoChaojun Duan
Oct 11, 2020·Cells·Magdalena IzdebskaAlina Grzanka
Jan 6, 2021·Molecular Cancer·Xiaoxu WeiZhaoyang Zeng
May 1, 2021·Cancers·Dorina BelottiGiulia Taraboletti
Aug 8, 2021·Cells·Gabriela Morales-GuadarramaLorenza Díaz
Aug 13, 2021·Frontiers in Oncology·Hui WangFengfeng Cai
Nov 3, 2021·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Nazila Fathi MaroufiMohammad Nouri

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Methods Mentioned

BETA
nuclear translocation
Flow
Assay
flow cytometry
reverse transcription PCR
biopsy
confocal microscopy
pulldown

Software Mentioned

ImageJ
FlowJo
GraphPad Prism
SPSS

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