VEGF165 requires extracellular matrix components to induce mitogenic effects and migratory response in breast cancer cells

Bone sialoprotein (BSP) has become a target in breast cancer research as it is associated with tumor progression and metastasis. The mechanisms underlying the regulation of BSP expression have been largely elusive. Given that BSP is involved in the homing of cancer cells in bone metastatic niches, we addressed regulatory effects of proteolytic cleavage and extracellular matrix components on BSP expression and distribution in cell culture models. Therefore, MDA-MB-231 human breast cancer cells were kept in 2D and 3D spheroid cultures and exposed to basement membrane extract in the presence or absence of matrix metalloproteinase 9 or the non-polar protease, dispase. Confocal imaging of immunofluorescence samples stained with different antibodies against human BSP demonstrated a strong inducing effect of basement membrane extract on anti-BSP immunofluorescence. Similarly, protease incubation led to acute upregulation of anti-BSP immunofluorescence signals, which was blocked by cycloheximide, suggesting de novo formation of BSP. In summary, our data show that extracellular matrix components play an important function in regulating BSP expression and hint at mechanisms for the formation of bone-associated metastasis in breast cancer that might involve local control of BSP levels by extracellular matrix degradation and release of growth factors.

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10568 ◽

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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A Benzochalcone Derivative, (E)-1-(2-hydroxy-6-methoxyphenyl)-3-(naphthalen-2-yl)prop-2-en-1-one (DK-512), Inhibits Tumor Invasion through Inhibition of the TNFα-Induced NF-κB/MMP-9 Axis in MDA-MB-231 Breast Cancer Cells

Journal of Chemistry ◽

10.1155/2016/4921717 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8

Author(s):

Soon Young Shin ◽

Chang Gun Kim ◽

Seunghyun Ahn ◽

You Jung Jung ◽

Dongsoo Koh ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Tumor Invasion ◽

Breast Cancer Cells ◽

Three Dimensional ◽

Extracellular Matrix Components ◽

System Tumor

Tumor invasion is a critical step in tumor metastasis. In this study, we synthesized a novel benzochalcone derivative, (E)-1-(2-hydroxy-6-methoxyphenyl)-3-(naphthalen-2-yl) prop-2-en-1-one (DK-512), and characterized its effects on tumor invasion and its mechanism of action. We found that DK-512 strongly inhibited invasion of metastatic MDA-MB-231 breast cancer cells as revealed by a three-dimensional spheroid culture system. Tumor invasion and metastasis require disruption of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is an endopeptidase that degrades extracellular matrix components. DK-512 significantly reduced tumor necrosis factor-α- (TNFα-) induced MMP-9 mRNA expression through the inhibition of RelA nuclear factor- (NF-)κB transcription factor. As our study was assessedin vitro, further works aboutin vivoefficacy of DK-512 are needed to gain further insights into whether DK-512 could be utilized as a scaffold for the development of antimetastatic agents for breast cancer.

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The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

Journal of Biological Chemistry ◽

10.1074/jbc.m114.612754 ◽

2015 ◽

Vol 290 (14) ◽

pp. 8722-8733 ◽

Cited By ~ 23

Author(s):

Raju R. Rayavarapu ◽

Brendan Heiden ◽

Nicholas Pagani ◽

Melissa M. Shaw ◽

Sydney Shuff ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Positive Breast Cancer

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Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells

Oncology Reports ◽

10.3892/or.13.4.745 ◽

2005 ◽

Cited By ~ 1

Author(s):

F. Vasaturo ◽

C. Malacrino ◽

E. Sallusti ◽

G. Coppotelli ◽

P. Birarelli ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Induced Apoptosis

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Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells

Oncology Reports ◽

10.3892/or.13.5.965 ◽

2005 ◽

Author(s):

K. Hokeness ◽

L. Qiu ◽

M. Vezeridis ◽

B. Yan ◽

S. Mehta ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Induced Apoptosis

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Efficient and simple approach to in vitro culture of primary epithelial cancer cells

Bioscience Reports ◽

10.1042/bsr20160208 ◽

2016 ◽

Vol 36 (6) ◽

Cited By ~ 10

Author(s):

Karolina Janik ◽

Marta Popeda ◽

Joanna Peciak ◽

Kamila Rosiak ◽

Maciej Smolarz ◽

...

Keyword(s):

Extracellular Matrix ◽

In Vitro Culture ◽

Cancer Cells ◽

Simple Approach ◽

Primary Cell ◽

Epithelial Cancer ◽

Extracellular Matrix Components ◽

Matrix Components ◽

Cell Medium

Primary breast and prostate epithelial cancer cells may be efficiently cultured in vitro using simple and easily validatable approach–plates coated with a mixture of extracellular matrix components and tissue-specific primary cell medium.

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