Cancer-associated fibroblasts induce trastuzumab resistance in HER2 positive breast cancer cells

2015 ◽  
Vol 11 (4) ◽  
pp. 1029-1040 ◽  
Author(s):  
Yan Mao ◽  
Yuzi Zhang ◽  
Qing Qu ◽  
Meizhong Zhao ◽  
Ying Lou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Associated Fibroblasts ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

CAFs isolated from HER2+ patients secreted higher levels of IL6 which expanded cancer stem cells and activated multiple pathways, then induced trastuzumab resistance in HER2 positive breast cancer cells.

scholarly journals Neuromedin U to increase IL-6 levels and to expand cancer stem cells in HER2-positive breast cancer cells.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 614-614
Author(s):  
Vanesa Gabriela Martinez ◽  
Sweta Rani ◽  
Claire Corcoran ◽  
John Crown ◽  
Lorraine O'Driscoll
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

CD44 expression contributes to trastuzumab resistance in HER2-positive breast cancer cells

2015 ◽  
Vol 151 (3) ◽  
pp. 501-513 ◽  
Author(s):  
Delphine R. Boulbes ◽  
Gaurav B. Chauhan ◽  
Quanri Jin ◽  
Chandra Bartholomeusz ◽  
Francisco J. Esteva
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Cd44 Expression ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells

2021 ◽  
Author(s):  
Jun Hua ◽  
Zhe Zhang ◽  
Lili Zhang ◽  
Yan Sun ◽  
Yuan Yuan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Neoadjuvant Therapy ◽  
Needle Biopsy ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
Trastuzumab Therapy ◽  
Positive Breast Cancer

Abstract Purpose This study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment. Methods 32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab. Results UCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis. Conclusion Taken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.

scholarly journals Dual inhibition of IGF1R and ER enhances response to trastuzumab in HER2 positive breast cancer cells

2017 ◽  
Vol 50 (6) ◽  
pp. 2221-2228 ◽  
Author(s):  
Martina S.J. Mcdermott ◽  
Alexandra Canonici ◽  
Laura Ivers ◽  
Brigid C. Browne ◽  
Stephen F. Madden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Dual Inhibition ◽  
Positive Breast Cancer

scholarly journals Linc01638 Promotes Tumorigenesis in HER2+ Breast Cancer

2018 ◽  
Vol 19 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Peng Liu ◽  
Hailin Tang ◽  
Jiali Wu ◽  
Xingsheng Qiu ◽  
Yanan Kong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Her2 Positive ◽  
Mouse Xenograft ◽  
Her2 Positive Breast Cancer ◽  
Mouse Xenograft Model ◽  
Positive Breast Cancer

Background: Long non-coding RNAs play crucial roles in various biological activities and diseases. The role of long intergenic non-coding RNA01638 (linc01638) in breast cancer, especially in HER2-positive breast cancer, remains largely unknown. Objective: To investigate the effect of linc01638 on tumorigenesis in HER2-positive breast cancer. </P><P> Methods: We first used qRT-PCR to detect linc01638 expression in HER2-positive breast cancer cells and tissues. Then we analyzed the effects of linc01638 expression in HER2-positive breast cancer cells through cell apoptosis assay, cell proliferation assay, colony formation assay, and cell invasion assay. We conducted mouse xenograft model to further confirm the role of linc01638 in HER2-positive breast cancer. Moreover, we used Western blot and IHC analysis to access the effect of linc01638 on DNMTs, BRCA1 and PTEN expressions in transplanted tumors. Results: Linc01638 was found to be remarkably overexpressed in HER2-positive breast cancer cells and tissues. Suppression of linc01638 enhanced cell apoptosis, as well as inhibited the growth and invasiveness of HER2-positive breast cancer cells in vitro and tumor progression and metastasis in vivo. Furthermore, inhibition of linc01638 by shRNA attenuated expression of DNMT1, DNMT3a, and DNMT3b, and promoted expression of BRCA1 and PTEN in HER2-positive breast cancer cells and mouse xenograft models. Linc01638 might be a promising biomarker and therapeutic target for treatment of HER2-positive breast cancer.

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