scholarly journals Inhibition of Metastatic Potential in Breast CarcinomaIn VivoandIn Vitrothrough Targeting VEGFRs and FGFRs

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ming-Hsien Chien ◽  
Liang-Ming Lee ◽  
Michael Hsiao ◽  
Lin-Hung Wei ◽  
Chih-Hau Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Invasive Breast Cancer ◽  
Cancer Metastasis ◽  
Lymphatic Endothelial Cells ◽  
Multikinase Inhibitor ◽  
Invasive Breast Cancer Cell

Angiogenesis and lymphangiogenesis are considered to play key roles in tumor metastasis. Targeting receptor tyrosine kinases essentially involved in the angiogenesis and lymphangiogenesis would theoretically prevent cancer metastasis. However, the optimal multikinase inhibitor for metastasis suppression has yet to be developed. In this study, we evaluated the effect of NSTPBP 0100194-A (194-A), a multikinase inhibitor of vascular endothelial growth factor receptors (VEGFRs)/fibroblast growth factor receptors (FGFRs), on lymphangiogenesis and angiogenesis in a mammary fat pad xenograft model of the highly invasive breast cancer cell line 4T1-Luc+. We investigated the biologic effect of 194-A on various invasive breast cancer cell lines as well as endothelial and lymphatic endothelial cells. Intriguingly, we found that 194-A drastically reduced the formation of lung, liver, and lymph node metastasis of 4T1-Luc+and decreased primary tumor growth. This was associated with significant reductions in intratumoral lymphatic vessel length (LVL) and microvessel density (MVD). 194-A blocked VEGFRs mediated signaling on both endothelial and lymphatic endothelial cells. Moreover, 194-A significantly inhibited the invasive capacity induced by VEGF-C or FGF-2in vitroin both 4T1 and MDA-MB231 cells. In conclusion, these experimental results demonstrate that simultaneous inhibition of VEGFRs/FGFRs kinases may be a promising strategy to prevent breast cancer metastasis.

Isolated Tumor Cells in Sentinel Lymph Nodes of Invasive Breast Cancer: Cell Displacement or Metastasis?

2014 ◽  
Vol 20 (5) ◽  
pp. 502-507 ◽  
Author(s):  
Jean-Christophe Tille ◽  
Pierre Loubeyre ◽  
Alexandre Bodmer ◽  
Anne-Sophie Jannot Berthier ◽  
Alexandre Rozenholc ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Invasive Breast Cancer ◽  
Sentinel Lymph Nodes ◽  
Isolated Tumor Cells ◽  
Invasive Breast Cancer Cell

scholarly journals Chlortetracycline, a Novel Arf Inhibitor That Decreases the Arf6-Dependent Invasive Properties of Breast Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 969
Author(s):  
Eric Macia ◽  
Monserrat Vazquez-Rojas ◽  
Alessia Robiolo ◽  
Racha Fayad ◽  
Sophie Abélanet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Invasive Breast Cancer ◽  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Breast Cancer Cell Lines ◽  
Metastatic Tumour ◽  
Invasive Breast Cancer Cell

Breast cancer is a major disease for women worldwide, where mortality is associated with tumour cell dissemination to distant organs. While the number of efficient anticancer therapies increased in the past 20 years, treatments targeting the invasive properties of metastatic tumour cells are still awaited. Various studies analysing invasive breast cancer cell lines have demonstrated that Arf6 is an important player of the migratory and invasive processes. These observations make Arf6 and its regulators potential therapeutic targets. As of today, no drug effective against Arf6 has been identified, with one explanation being that the activation of Arf6 is dependent on the presence of lipid membranes that are rarely included in drug screening. To overcome this issue we have set up a fluorescence-based high throughput screening that follows overtime the activation of Arf6 at the surface of lipid membranes. Using this unique screening assay, we isolated several compounds that affect Arf6 activation, among which the antibiotic chlortetracycline (CTC) appeared to be the most promising. In this report, we describe CTC in vitro biochemical characterization and show that it blocks both the Arf6-stimulated collective migration and cell invasion in a 3D collagen I gel of the invasive breast cancer cell line MDA-MB-231. Thus, CTC appears as a promising hit to target deadly metastatic dissemination and a powerful tool to unravel the molecular mechanisms of Arf6-mediated invasive processes.

scholarly journals The pan-histone deacetylase inhibitor LBH589 (panobinostat) alters the invasive breast cancer cell phenotype

2013 ◽  
Vol 44 (3) ◽  
pp. 700-708 ◽  
Author(s):  
NICOLETTA FORTUNATI ◽  
FRANCESCA MARANO ◽  
ANDREA BANDINO ◽  
ROBERTO FRAIRIA ◽  
MARIA GRAZIELLA CATALANO ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histone Deacetylase ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Invasive Breast Cancer ◽  
Histone Deacetylase Inhibitor ◽  
Cell Phenotype ◽  
Invasive Breast Cancer Cell ◽  
Deacetylase Inhibitor

scholarly journals Fibronectin Affects Transient MMP2 Gene Expression through DNA Demethylation Changes in Non-Invasive Breast Cancer Cell Lines

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e105806 ◽  
Author(s):  
Isabela T. Pereira ◽  
Edneia A. S. Ramos ◽  
Erico T. Costa ◽  
Anamaria A. Camargo ◽  
Graciele C. M. Manica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Invasive Breast Cancer ◽  
Dna Demethylation ◽  
Breast Cancer Cell Lines ◽  
Invasive Breast Cancer Cell ◽  
Non Invasive

scholarly journals Cancer-Derived VEGF-C Increases Chemokine Production in Lymphatic Endothelial Cells to Promote CXCR2-Dependent Cancer Invasion and MDSC Recruitment

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1120
Author(s):  
Jing-Yi Chen ◽  
You-Syuan Lai ◽  
Pei-Yi Chu ◽  
Shih-Hsuan Chan ◽  
Lu-Hai Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Cancer Invasion ◽  
Lymphatic Endothelial Cells ◽  
Chemokine Production ◽  
Factor C

Breast cancer-derived vascular endothelial growth factor-C (VEGF-C) has been shown to enhance lymphangiogenesis in lymph nodes to accelerate cancer metastasis. However, the remodeling of lymph node microenvironments by VEGF-C remains elusive. By in vivo selection, we established a subline (named as “LC”) with strong lymphatic tropism and high VEGF-C expression from the human MDA-MB-231 breast cancer cell line. Co-culture with LC cells or treatment with LC-conditioned medium upregulated the expression of CXC chemokines in lymphatic endothelial cells (LECs), which could be inhibited by pre-incubation with VEGF-C-neutralizing antibodies and VEGFR3 inhibitors. The chemokines produced by LECs enhanced recruitment of myeloid-derived suppressor cells (MDSCs) to tumor-draining and distant lymph nodes in tumor-bearing mice. Treatment with a CXCR2 inhibitor after tumor cell inoculation dramatically decreased the number of MDSCs in lymph nodes, suggesting the importance of the chemokine/CXCR2 signaling axis in MDSC recruitment. In addition, LEC-released chemokines also stimulated the expression of serum amyloid A1 (SAA1) in cancer cells, enhancing their lymphatic invasion by increasing VE-cadherin phosphorylation, junction disruption, and vascular permeability of LECs. Clinical sample validation confirmed that SAA1 expression was associated with increased lymph node metastasis. Collectively, we reveal a novel mechanism by which cancer cell-derived VEGF-C remodels lymphovascular microenvironments by regulating chemokine production in LECs to promote cancer invasion and MDSC recruitment. Our results also suggest that inhibition of CXCR2 is effective in treating lymphatic metastasis.

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