Influence of basement membrane molecules on directional migration of human breast cell lines in vitro

1991 ◽  
Vol 98 (3) ◽  
pp. 395-401
Author(s):  
P.J. Coopman ◽  
M.E. Bracke ◽  
J.C. Lissitzky ◽  
G.K. De Bruyne ◽  
FM Van Roy ◽  
...  

Spheroidal cell aggregates were prepared from four tumorigenic human breast cell lines (HBL-100 and three MCF-7 variants). Cells from these aggregates were allowed to migrate towards lanes of basement membrane components coated on a glass substratum. Matrigel (reconstituted basement membrane) lanes permanently arrested the migration of one MCF-7 cell line, while migration of the others was permitted. Amongst several purified basement membrane constituents only laminin, not collagen type IV or fibronectin, was found to cause the same arrest of migration. Within the laminin molecule only the pepsin P1, not the elastase E8 fragment, efficiently arrested migration of that cell line. Although migration was inhibited by these components, time-lapse video recordings revealed that arrested cells still proliferated and actively ruffled on top of the coatings. These data suggest that, amongst several basement membrane components, laminin can function as a stop signal for cell migration. Within laminin, this activity seems to be mainly associated with the P1 fragment. We conclude that laminin is the major determinant of the barrier-function of the basement membrane, to which some cell types have become insensitive.

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Carmen Ortiz ◽  
Luisa Morales ◽  
Miguel Sastre ◽  
William E. Haskins ◽  
Jaime Matta

Sandalwood essential oil (SEO) is extracted fromSantalumtrees. Althoughα-santalol, a main constituent of SEO, has been studied as a chemopreventive agent, the genotoxic activity of the whole oil in human breast cell lines is still unknown. The main objective of this study was to assess the cytotoxic and genotoxic effects of SEO in breast adenocarcinoma (MCF-7) and nontumorigenic breast epithelial (MCF-10A) cells. Proteins associated with SEO genotoxicity were identified using a proteomics approach. Commercially available, high-purity, GC/MS characterized SEO was used to perform the experiments. The main constituents reported in the oil were (Z)-α-santalol (25.34%), (Z)-nuciferol (18.34%), (E)-β-santalol (10.97%), and (E)-nuciferol (10.46%). Upon exposure to SEO (2–8 μg/mL) for 24 hours, cell proliferation was determined by the MTT assay. Alkaline and neutral comet assays were used to assess genotoxicity. SEO exposure induced single- and double-strand breaks selectively in the DNA of MCF-7 cells. Quantitative LC/MS-based proteomics allowed identification of candidate proteins involved in this response: Ku70 (p=1.37E-2), Ku80 (p=5.8E-3), EPHX1 (p=3.3E-3), and 14-3-3ζ(p=4.0E-4). These results provide the first evidence that SEO is genotoxic and capable of inducing DNA single- and double-strand breaks in MCF-7 cells.


2006 ◽  
Vol 95 (2) ◽  
pp. 406-413 ◽  
Author(s):  
Bertrand Caëtano ◽  
Ludovic Le Corre ◽  
Nassera Chalabi ◽  
Laetitia Delort ◽  
Yves-Jean Bignon ◽  
...  

Breast cancer is the most common cancer in women and a significant cause of death. Mutations of the oncosuppressor genes BRCA1 and BRCA2 are associated with a hereditary risk of breast cancer, and dysregulation of their expression has been observed in sporadic cases. Soya isoflavones have been shown to inhibit breast cancer in studies in vitro, but associations between the consumption of isoflavone-containing foods and breast cancer risk have varied in epidemiological studies. Soya is a unique source of the phytoestrogens daidzein (4′,7-dihydroxyisoflavone) and genistein (4′,5,7-trihydroxyisoflavone), two molecules that are able to inhibit the proliferation of human breast cancer cells in vitro. The aim of the present study was to determine the effects of genistein (5μg/ml) and daidzein (20μg/ml) on transcription in three human breast cell lines (one dystrophic, MCF10a, and two malignant, MCF-7 and MDA-MB-231) after 72h treatment. The different genes involved in the BRCA1 and BRCA2 pathways (GADD45A, BARD1, JUN, BAX, RB1, ERα, ERβ, BAP1, TNFα, p53, p21Waf1/Cip1, p300, RAD51, pS2, Ki-67) were quantified by real-time quantitative RT-PCR, using the TaqMan method and an ABI Prism 7700 Sequence Detector (Applied Biosystems). We observed that, in response to treatment, many of these genes were overexpressed in the breast cancer cell lines (MCF-7 and MDA-MB-231) but not in the dystrophic cell line (MCF10a).


1987 ◽  
Author(s):  
D Arnoux ◽  
B Boutière ◽  
N Pourreau-Schneider ◽  
P Martin ◽  
J Sampol

Plasminogen activators (PA)may play an important role in the regulation of enzyme activation relative to basement membrane degradation associated with the invasive growth of tumors. In order to acquire a better understanding of the complex cascade reactions leading to the formation of plasmin, we have undertaken a comparative study of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators in cellular extracts of 20 human cancer cell lines (13 malignant melanomas, 6 breast adenocarcinomas and 1 vulvar carcinoma). Four malignant cell lines,showing various t-PA or u-PA activity levels, were selected to study the modulation of proteolytic activity by laminin and fibronectin, major components of basal membrane. This study was performed in cellular extracts and conditioned medium. Our results showed that melanoma cells have high t-PA activity preferentially released into the culture medium. On the vulvar cell line, A 431, u-PA activity predominates and is also secreted into the medium. In contrast, breast cancer cells MCF-7 and MDA show u-PA activity, mostly recovered in the cellular extracts. An enhancement of respective PA activities occurs when cells are cultured on fibronectin or laminin, varying with the nature of the cell line.Additional studies are needed to precise interrelation between tumor cells, basement membrane components and PA activities and the potential significance of proteolytic activities as markers of malignancy and invasive capacity.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Vincenza Barresi ◽  
Carmela Bonaccorso ◽  
Domenico A. Cristaldi ◽  
Maria N. Modica ◽  
Nicolò Musso ◽  
...  

Recent drug discovery efforts are highly focused towards identification, design, and synthesis of small molecules as anticancer agents. With this aim, we recently designed and synthesized novel compounds with high efficacy and specificity for the treatment of breast tumors. Based on the obtained results, we constructed a Volsurf+ (VS+) model using a dataset of 59 compounds able to predict the in vitro antitumor activity against MCF-7 cancer cell line for new derivatives. In the present paper, in order to further verify the robustness of this model, we report the results of the projection of more than 150 known molecules and 9 newly synthesized compounds. We predict their activity versus MCF-7 cell line and experimentally verify the in silico results for some promising chosen molecules in two human breast cell lines, MCF-7 and MDA-MB-231.


BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin Morgan ◽  
Colette Meyer ◽  
Nicola Miller ◽  
Andrew H Sims ◽  
Ilgin Cagnan ◽  
...  

1995 ◽  
Vol 35 (2) ◽  
pp. 211-220 ◽  
Author(s):  
Lisa D. Laury-Kleintop ◽  
Elizabeth C. Coronel ◽  
Marianne K. Lange ◽  
Thomas Tachovsky ◽  
Santo Longo ◽  
...  

2015 ◽  
Vol 67 (8) ◽  
pp. 1344-1356 ◽  
Author(s):  
Hanna Szaefer ◽  
Violetta Krajka-Kuźniak ◽  
Barbara Licznerska ◽  
Agnieszka Bartoszek ◽  
Wanda Baer-Dubowska

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