scholarly journals Overcoming Trastuzumab Resistance in HER2-Overexpressing Breast Cancer Cells by Using a Novel Celecoxib-Derived Phosphoinositide-Dependent Kinase-1 Inhibitor

2006 ◽  
Vol 70 (5) ◽  
pp. 1534-1541 ◽  
Author(s):  
Ping-Hui Tseng ◽  
Yu-Chieh Wang ◽  
Shu-Chuan Weng ◽  
Jing-Ru Weng ◽  
Chang-Shi Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Trastuzumab Resistance ◽  
Phosphoinositide Dependent Kinase

scholarly journals Involvement of microRNA-146a in trastuzumab resistance of HER2+ breast cancer cells

2017 ◽  
Vol 28 ◽  
pp. vii25-vii26
Author(s):  
P. Cabello ◽  
J. Forés ◽  
E. Tormo ◽  
B. Pineda ◽  
A. Adam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Trastuzumab Resistance ◽  
Her2 Breast Cancer

scholarly journals Loss of STAT6 leads to anchorage-independent growth and trastuzumab resistance in HER2+ breast cancer cells

PLoS ONE ◽  
2020 ◽  
Vol 15 (6) ◽  
pp. e0234146 ◽  
Author(s):  
Molly DiScala ◽  
Matthew S. Najor ◽  
Timothy Yung ◽  
Deri Morgan ◽  
Abde M. Abukhdeir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Trastuzumab Resistance ◽  
Anchorage Independent Growth ◽  
Her2 Breast Cancer

scholarly journals Targeting the MUC1-C oncoprotein downregulates HER2 activation and abrogates trastuzumab resistance in breast cancer cells

Oncogene ◽  
2013 ◽  
Vol 33 (26) ◽  
pp. 3422-3431 ◽  
Author(s):  
D Raina ◽  
Y Uchida ◽  
A Kharbanda ◽  
H Rajabi ◽  
G Panchamoorthy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Trastuzumab Resistance

Downregulation of Erbin in Her2-overexpressing breast cancer cells promotes cell migration and induces trastuzumab resistance

2013 ◽  
Vol 56 (1-2) ◽  
pp. 104-112 ◽  
Author(s):  
Dan Liu ◽  
Ming Shi ◽  
Chenyang Duan ◽  
Hongyu Chen ◽  
Yabin Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Trastuzumab Resistance

Extracellular matrix and breast cancer cells' response to trastuzumab: The role of glycosaminoglycans, heparanases, and syndecan-1.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10568-10568
Author(s):  
Maria Aparecida Silva Pinhal ◽  
Eloah Rabello Suarez ◽  
Helena Bonciani Nader ◽  
Auro Del Giglio
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cell Surface ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antibody Activity ◽  
Trastuzumab Resistance ◽  
Mcf7 Cells ◽  
Her2 Positive ◽  
Extracellular Matrix Components

10568 Background: Trastuzumab is an antibody anti-epidermal growth factor 2 receptor (HER2), which improves disease-free and overall survival in HER2 positive breast cancer. Nevertheless, many patients become resistant to this treatment. Heparanase (HPSE) is an enzyme that is responsible for removal of heparan sulfate (HS) chains from proteoglycans, generating free oligosaccharides that modulate many physiopathological functions, including tumor developing. We have analyzed whether some extracellular matrix components influence trastuzumab efficacy. Methods: Heparanase-1 (HPSE-1) overexpression effect was analyzed using MCF7 cells stable transfected with HPSE-1 cDNA (MCF7-HPSE-1). HPSE-1, HPSE-2, Syndecan-1 (Syn-1) and HER2 expression, HPSE-1 activity and cell viability were evaluated in different breast cancer cells treated or not with trastuzumab. The glycosaminoglycans synthesis and shedding were also evaluated. Trastuzumab and HS binding were analyzed by confocal microscopy and Fluorescence Resonance Energy Transfer (FRET). Results: MCF7 transfected with HPSE-1 cDNA becomes completely resistant to trastuzumab. HS affinity by Trastuzumab was then tested, showing that they bind in high levels and this binding is necessary to antibody activity. In MCF7 cells, trastuzumab decreases HPSE-1, HPSE-2, HER2 and Syn-1 mRNA expression, while in MCF7-HPSE-1 the antibody increases the expression of these molecules. Conclusions: Our results have demonstrated that an ideal concentration of HS in cell surface, regulated by trastuzumab, is necessary to its action, beyond HER2 high levels. High HS concentration at cell surface enhances the antibody amount disposable to interact with HER2 in cell surface, determining breast cancer cells susceptibility to trastuzumab. These new insights could be useful when devising strategies for overcoming trastuzumab resistance in HER2 positive cancers. Supported by FAPESP, CNPq, CAPES.

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