scholarly journals Targeting of GLUT5 for Transporter-Mediated Drug-Delivery Is Contingent upon Substrate Hydrophilicity

2021 ◽  
Vol 22 (10) ◽  
pp. 5073
Author(s):  
Nazanin Nahrjou ◽  
Avik Ghosh ◽  
Marina Tanasova
Keyword(s):  
Cancer Cells ◽  
Normal Breast ◽  
Proof Of Concept ◽  
Drug Conjugates ◽  
High Fructose ◽  
Specific Cytotoxicity ◽  
Breast Cells ◽  
Substrate Tolerance ◽  
Bioactive Agents ◽  
Positive Breast Cancer

Specific link between high fructose uptake and cancer development and progression highlighted fructose transporters as potential means to achieve GLUT-mediated discrimination between normal and cancer cells. The gained expression of fructose-specific transporter GLUT5 in various cancers offers a possibility for developing cancer-specific imaging and bioactive agents. Herein, we explore the feasibility of delivering a bioactive agent through cancer-relevant fructose-specific transporter GLUT5. We employed specific targeting of GLUT5 by 2,5-anhydro-D-mannitol and investigated several drug conjugates for their ability to induce cancer-specific cytotoxicity. The proof-of-concept analysis was carried out for conjugates of chlorambucil (CLB) in GLUT5-positive breast cancer cells and normal breast cells. The cytotoxicity of conjugates was assessed over 24 h and 48 h, and significant dependence between cancer-selectivity and conjugate size was observed. The differences were found to relate to the loss of GLUT5-mediated uptake upon increased conjugate size and hydrophobicity. The findings provide information on the substrate tolerance of GLUT5 and highlight the importance of maintaining appropriate hydrophilicity for GLUT-mediated delivery.

Leptin Induces a Proliferative Response in Breast Cancer Cells but Not in Normal Breast Cells

2014 ◽  
Vol 66 (4) ◽  
pp. 645-655 ◽  
Author(s):  
Virginie Dubois ◽  
Thierry Jardé ◽  
Laetitia Delort ◽  
Hermine Billard ◽  
Dominique Bernard-Gallon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Proliferative Response ◽  
Breast Cancer Cells ◽  
Normal Breast ◽  
Breast Cells

scholarly journals Vascular endothelial growth factor encoded by Parapoxviruses can regulate metabolism and survival of triple negative breast cancer cells

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Dipayan Bose ◽  
Sagarika Banerjee ◽  
Rajnish Kumar Singh ◽  
Lyn M. Wise ◽  
Erle S. Robertson
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Normal Breast ◽  
Cancer Breast ◽  
Human Genes ◽  
Metabolic Gene Expression ◽  
Breast Cells

AbstractDysbiotic microbiomes are linked to many pathological outcomes including different metabolic disorders like diabetes, atherosclerosis and even cancer. Breast cancer is the second leading cause of cancer associated death in women, and triple negative breast cancer (TNBC) is the most aggressive type with major challenges for intervention. Previous reports suggested that Parapoxvirus signatures are one of the predominant dysbiotic viral signatures in TNBC. These viruses encode several genes that are homologs of human genes. In this study, we show that the VEGF homolog encoded by Parapoxviruses, can induce cell proliferation, and alter metabolism of breast cancer and normal breast cells, through alteration of MAPK-ERK and PI3K-AKT signaling. In addition, the activity of the transcription factor FoxO1 was altered by viral-encoded VEGF through activation of the PI3K-AKT pathway, leading to reprogramming of cellular metabolic gene expression. Therefore, this study provides new insights into the function of viral-encoded VEGFs, which promoted the growth of the breast cancer cells and imparted proliferative phenotype with altered metabolism in normal breast cells.

Adhesion Between Anti-EphA2 Antibody-Coated AFM Tips and Breast Cancer Cells

2009 ◽  
Vol 1237 ◽  
Author(s):  
Emily Paetzell ◽  
Andrew Bogorad ◽  
Juan Meng ◽  
Winston oluwole Soboyejo
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Adhesion Force ◽  
Normal Breast ◽  
Atomic Force ◽  
Afm Tips ◽  
Ligand Interactions ◽  
Breast Cells ◽  
Adhesive Interactions

AbstractThis paper presents the results of atomic force microscope (AFM) measurements of the adhesion force between MDA-MB-231 breast cancer cells and anti-EphA2 antibody-coated AFM tips. As a control, the adhesive interactions are measured between Hs578Bst normal breast cells and anti-EphA2 antibody-coated AFM tips. The measurements show conclusively that the adhesive forces to breast cancer cells are over five times greater than those to normal breast cells. The increase is attributed largely to the interactions between anti-EphA2 antibody and over-expressed EphA2 receptors that are revealed by the staining of receptor-ligand interactions. The implications of the results are discussed for the localized targeting and treatment of cancer with antibody-conjugated nanoparticles.

scholarly journals Combined p53- and PTEN-deficiency activates expression of mesenchyme homeobox 1 (MEOX1) required for growth of triple-negative breast cancer

2020 ◽  
Vol 295 (34) ◽  
pp. 12188-12202
Author(s):  
Mari Gasparyan ◽  
Miao-Chia Lo ◽  
Hui Jiang ◽  
Chang-Ching Lin ◽  
Duxin Sun
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Normal Breast ◽  
Luminal A ◽  
Tyrosine Kinase 2 ◽  
Breast Cells

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype for which effective therapies are unavailable. TNBC has a high frequency of tumor protein p53 (Tp53/p53)- and phosphatase and tensin homolog (PTEN) deficiencies, and combined p53- and PTEN-deficiency is associated with poor prognosis and poor response to anticancer therapies. In this study, we discovered that combined p53- and PTEN-deficiency in TNBC activates expression of the transcription factor mesenchyme homeobox 1 (MEOX1). We found that MEOX1 is expressed only in TNBC cells with frequent deficiencies in p53 and PTEN, and that its expression is undetectable in luminal A, luminal B, and HER2+ subtypes, as well as in normal breast cells with wild-type (WT) p53 and PTEN. Notably, siRNA knockdown of both p53 and PTEN activated MEOX1 expression in breast cancer cells, whereas individual knockdowns of either p53 or PTEN had only minimal effects on MEOX1 expression. MEOX1 knockdown abolished cell proliferation of p53- and PTEN-deficient TNBC in vitro and inhibited tumor growth in vivo, but had no effect on the proliferation of luminal and HER2+ cancer cells and normal breast cells. RNA-Seq and immunoblotting analyses showed that MEOX1 knockdown decreased expression of tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 5B (STAT5B), and STAT6 in p53- and PTEN-deficient TNBC cells. These results reveal the effects of combined p53- and PTEN-deficiency on MEOX1 expression and TNBC cell proliferation, suggesting that MEOX1 may serve as a potential therapeutic target for managing p53- and PTEN-deficient TNBC.

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