silicon and Neoplasm-Metastasis

Lactate, the main contributor to the acidic tumor microenvironment, not only promotes the proliferation of tumor cells, but also closely relates to tumor invasion and metastasis. Here, a tumor targeting nanoplatform, designated as Me&Flu@MSN@MnO

Topics: Antineoplastic Agents; Cell Line, Tumor; Fluvastatin; Folic Acid; Humans; Lactates; Manganese Compounds; Metformin; Nanoparticles; Neoplasm Metastasis; Neoplasms; Porosity; Silicon; Tumor Microenvironment

Detection of rare metastatic cells within a benign tumor is a key challenge to diagnose the cancerous stage of the patients tested by clinical human biopsy or pap smear samples. We have fabricated and tested a nanograssed silicon based bioelectronic device with the ability of detecting a few human colon invasive cancer cells (SW48) in a mixed cell culture of primary cancerous colon cells (HT29) without any biochemical labels. A discernible impedance change was elicited after the presence of 5% metastatic cells in the whole benign sample. The electric field penetration as well as current flow to metastatic cells is different from benign ones due to their different membrane dielectric parameters. Beta dispersion as one of intrinsic bioelectrical properties of the cell membrane in blocking the stimulating current flow in the range of kHz is the specific parameter involved in our diagnosis approach. It can reflect in-depth information about the dielectric properties and the pathological condition of a cell before and after metastatic transformation. Electrically active doped silicon nanograss structures owing to their superior nanocontacts with cell membrane can detect any slight variations in current being originated from the presence of rare metastatic cells on the surface of the sensing electrode. The experimental results revealed that bare doped silicon microelectrodes are incapable of resolving different grades of attached cells.

Topics: Biosensing Techniques; Cell Line, Tumor; Colon; Colonic Neoplasms; Electric Impedance; Equipment Design; Humans; Nanostructures; Neoplasm Metastasis; Neoplasm Staging; Silicon; Tumor Cells, Cultured

It is now well established that tumor cell invasion through tissue is strongly regulated by the microstructural and mechanical properties of the extracellular matrix (ECM). However, it remains unclear how these physical microenvironmental inputs are jointly processed with oncogenic lesions to drive invasion. In this study, we address this open question by combining a microfabricated polyacrylamide channel (μPAC) platform that enables independent control of ECM stiffness and confinement with an isogenically-matched breast tumor progression series in which the oncogenes ErbB2 and 14-3-3ζ are overexpressed independently or in tandem. We find that increasing channel confinement and overexpressing ErbB2 both promote cell migration to a similar degree when other parameters are kept constant. In contrast, 14-3-3ζ overexpression slows migration speed, and does so in a fashion that dwarfs effects of ECM confinement and stiffness. We also find that ECM stiffness dramatically enhances cell motility when combined with ErbB2 overexpression, demonstrating that biophysical cues and cell-intrinsic parameters promote cell invasion in an integrative manner. Morphometric analysis of cells inside the μPAC platform reveals that the rapid cell migration induced by narrow channels and ErbB2 overexpression are both accompanied by increased cell polarization. Disruption of this polarization occurs by pharmacological inhibition of Rac GTPase phenocopies 14-3-3ζ overexpression by reducing cell polarization and slowing migration. By systematically measuring migration speed as a function of matrix stiffness and confinement, we also quantify for the first time the sensitivity of migration speed to microchannel properties and transforming potential. These results demonstrate that oncogenic lesions and ECM biophysical properties can synergistically interact to drive invasive migration, and that both inputs may act through common molecular mechanisms to enhance migration speed.

Topics: 14-3-3 Proteins; Acrylic Resins; Cell Culture Techniques; Cell Line, Tumor; Cell Movement; Cell Transformation, Neoplastic; Extracellular Matrix; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Microscopy, Confocal; Microscopy, Phase-Contrast; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; rac GTP-Binding Proteins; Receptor, ErbB-2; Silicon

Ensemble-decision aliquot ranking (eDAR) is a sensitive and high-throughput method to analyze circulating tumor cells (CTCs) from peripheral blood. Here, we report the next generation of eDAR, where we designed and optimized a new hydrodynamic switching scheme for the active sorting step in eDAR, which provided fast cell sorting with an improved reproducibility and stability. The microfluidic chip was also simplified by incorporating a functional area for subsequent purification using microslits fabricated by standard lithography method. Using the reported second generation of eDAR, we were able to analyze 1 mL of whole-blood samples in 12.5 min, with a 95% recovery and a zero false positive rate (n = 15).

Topics: Cell Line, Tumor; Cell Separation; Humans; Hydrodynamics; Microfluidic Analytical Techniques; Neoplasm Metastasis; Neoplastic Cells, Circulating; Pancreatic Neoplasms; Silicon