flow-cytometric-detection-newly-formed-breast-cancer-stem-cell-like

Flow Cytometric Detection of Newly-formed Breast Cancer Stem Cell-like Cells After Apoptosis Reversal

Cancer recurrence has long been studied by oncologists while the underlying mechanisms remain unclear. Recently, we and others found that a phenomenon ...

The Chinese University of Hong Kong

Cardiac pacemaking is a complex phenomenon that is not completely understood. Canonical transient receptor potential isoform 3 (TRPC3) channel is a cation channel that permeates both Ca(2+) and Na(+). TRPC3 was previously found to express in adult cardiomyocytes. However, its role in cardiac pacemaking is unexplored. Here we used mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) to investigate whether TRPC3 regulates the spontaneous automaticity and the underlying mechanism involved.

TRPC3 regulates the automaticity of embryonic stem cell-derived cardiomyocytes.

It has long been a puzzle in cancer treatment that despite the initial appearance of apoptosis, the process could be reversed in some cancer cells and often results in more aggressive tumors and metastasis. The mechanism for this recurrence is yet unknown. Here we report that human mammary carcinoma cells induced to undergo apoptosis could recover with increased tumorigenicity in vitro and in vivo, and induced lymph node metastasis. Specifically, the reversed cells underwent epithelial-to-mesenchymal transitions in the primary tumors in situ, and mesenchymal-to-epithelial transitions in the metastatic cells. Flow cytometry confirmed an elevated percentage of cells carrying cancer stem cells (CSCs) markers (CD44/CD24) in the reversed breast cancer cell population, with hypomethylated CD44 promoters and hypermethylated CD24 promoters. More importantly, CSCs were generated anew from non-stem cancer cells after apoptosis reversal possibly through epigenetic modifications. The results from this study can open doors to discovering more effective cancer treatments by suppressing apoptosis reversal.

Apoptosis Reversal Promotes Cancer Stem Cell-Like Cell Formation.

A growing number of epidemiological surveys show that PM is an important promoter for the cardiovascular dysfunction induced by atmospheric pollution. PM is a complex mixture of solid and liquid airborne particles and its components determine the health risk of PMto a great extent. However, the individual cardiotoxicities of different PM fractions are still unclear, especially in the cellular level. Here we used the neonatal rat cardiomyocytes (NRCMs) to evaluate the cardiac toxicity of PM exposure. The cytotoxicities of Total-PM, water soluble components of PM (WS-PM) and water insoluble components of PM (WIS-PM), which include the cell viability, cell membrane damage, reactive oxygen species (ROS) generation, were examined with NRCMs in vitro. The results indicated that Total-PM or WIS-PM exposure significantly decreased the cell viability, induced the cell membrane damage and increased the ROS level in NRCMs at concentrations above 50 µg/mL. However, WS-PM exposure could induce the cytotoxicity on NRCMs until the concentration of WS-PM was raised to a higher concentration (75 µg/mL). Furthermore, the DNA damage was detected in NRCMs after 48 h of exposure with Total-PM, WS-PM or WIS-PM (75 µg/mL) and the adverse effects on mitochondrial function and action potentials of NRCMs were detected only both in the Total-PM and WIS-PM treatment group. In summary, our project not only estimates the risk of PM on cardiac cells but also reveal that Total-PM and WIS-PM exposure were predominantly associated with the functional cardiotoxicities in NRCMs.

Suk-Ying Tsang

School of Life Sciences,
State Key Laboratory of Agrobiotechnology,
Key Laboratory for Regenerative Medicine,
Ministry of Education,
Centre for Novel Biomaterials,
Key Laboratory for Regenerative Medicine, Ministry of Education

The Chinese University of Hong Kong

Flow Cytometric Detection of Newly-formed Breast Cancer Stem Cell-like Cells After Apoptosis Reversal