silicon and Triple-Negative-Breast-Neoplasms

Breast cancer is the most common type of cancer observed in women. Communication with the tumor microenvironment allows invading breast cancer cells, such as triple negative breast cancer cells, to adapt to specific substrates. The substrate topography modulates the cellular behavior among other factors. Several different materials and micro/nanofabrication techniques have been employed to develop substrates for cell culture. Silicon-based substrates present a lot of advantages as they are amenable to a wide range of processing techniques and they permit rigorous control over the surface structure. We investigate and compare the response of the triple negative breast cancer cells (MDA-MB-231) on laser-patterned silicon substrates with two different topographical scales, i.e., the micro- and the nanoscale, in the absence of any other biochemical modification. We develop silicon surfaces with distinct morphological characteristics by employing two laser systems with different pulse durations (nanosecond and femtosecond) and different processing environments (vacuum, SF

Topics: Cell Adhesion; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Female; Humans; Lasers; Silicon; Triple Negative Breast Neoplasms; Tumor Microenvironment

Cancer cells have high rates of glycolysis and lactic acid fermentation in order to fuel accelerated rates of cell division (Warburg effect). Here, we present a strategy for merging cancer and yeast metabolism to remove pyruvate, a key intermediate of cancer cell metabolism, and produce the toxic compound acetaldehyde. This approach was achieved by administering the yeast enzyme pyruvate decarboxylase to triple negative breast cancer cells. To overcome the challenges of protein delivery, a nanoparticle-based system consisting of cationic lipids and porous silicon were employed to obtain efficient intracellular uptake. The results demonstrate that the enzyme therapy decreases cancer cell viability through production of acetaldehyde and reduction of lactic acid fermentation.

Topics: Acetaldehyde; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Drug Carriers; Drug Compounding; Energy Metabolism; Female; Fermentation; Glycolysis; Humans; Lactic Acid; Lipids; Nanoparticles; Porosity; Pyruvate Decarboxylase; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Silicon; Triple Negative Breast Neoplasms

Triple negative breast cancer (TNBC) is highly aggressive and has a poor prognosis when compared to other molecular subtypes. In particular, the claudin-low subtype of TNBC exhibits tumor-initiating/cancer stem cell like properties. Here, we seek to find new biomarkers to discriminate different forms of TNBC by characterizing their bioimpedance. A customized bioimpedance sensor with four identical branched microelectrodes with branch widths adjusted to accommodate spreading of individual cells was fabricated on silicon and pyrex/glass substrates. Cell analyses were performed on the silicon devices which showed somewhat improved inter-electrode and intra-device reliability. We performed detailed analysis of the bioimpedance spectra of four TNBC cell lines, comparing the peak magnitude, peak frequency and peak phase angle between claudin-low TNBC subtype represented by MDA-MB-231 and Hs578T with that of two basal cells types, the TNBC MDA-MB-468, and an immortalized non-malignant basal breast cell line, MCF-10A. The claudin-low TNBC cell lines showed significantly higher peak frequencies and peak phase angles than the properties might be useful in distinguishing the clinically significant claudin-low subtype of TNBC.

Topics: Cell Line, Tumor; Cell Survival; Claudins; Electric Impedance; Female; Humans; Microelectrodes; Microscopy, Confocal; Microscopy, Electron, Scanning; Models, Biological; Neoplastic Stem Cells; Reproducibility of Results; Silicon; Triple Negative Breast Neoplasms