Emerging signals regulating liver tumor initiating cells

Tumor initiating cells(TICs)have been identified as cells that account for tumor heterogeneity.Recent studies demonstrated that genes controlling stem cell biology play key roles in maintaining TICs and promote their development into cancer.In this review,we summarize findings from human and animal studies that indicate the presence of TICs during liver cancer development.Markers identified for liver development and regeneration are used to identify liver cancer TICs.Expression of these markers is often upregulated in human hepatocellular carcinoma(HCC)specimen.Using flow cytometry analysis and lineage tracing approaches,the presence of TICs is confirmed.Expression of TIC markers and the presence of TICs are also observed in genetically modified animals that target genes that are frequently altered in human HCC.The presence of these TICs represents a major challenge for therapeutic development.Elucidating signals that can regulate the fate,transformation and growth of liver TICs is an emerging need in liver research.Sex-determining region Y-box 9(SOX9)has recently become an important marker for liver TICs.Here,we summarize the role of SOX9 in TICs and its potential interaction with other signals.This includes the Notch-Numb signal that controls asymmetrical-symmetrical cell division,Wnt-b-catenin signal that maintains cell fate and transforming growth factor(TGF)-b signal that acts as upstream inducers.

Therapeutic implications of colon cancer stem cells

Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.

Murine hepatocellular carcinoma derived stem cells reveal epithelial-to-mesenchymal plasticity

AIM To establish a model to enrich and characterize stemlike cells from murine normal liver and hepatocellular carcinoma(HCC) cell lines and to further investigate stem-like cell association with epithelial-to-mesenchymal transition(EMT).METHODS In this study,we utilized a stem cell conditioned serumfree medium to enrich stem-like cells from mouse HCC and normal liver cell lines,Hepa 1-6 and AML12,respectively.We isolated the 3-dimensional spheres and assessed their stemness characteristics by evaluating theRNA levels of stemness genes and a cell surface stem cell marker by quantitative reverse transcriptase-PCR(q RTPCR).Next,we examined the relationship between stem cells and EMT using q RT-PCR.RESULTS Three-dimensional spheres were enriched by culturing murine HCC and normal hepatocyte cell lines in stem cell conditioned serum-free medium supplemented with epidermal growth factor,basic fibroblast growth factor and heparin sulfate.The 3-dimensional spheres had enhanced stemness markers such as Klf4 and Bmi1 and hepatic cancer stem cell(CSC) marker Cd44 compared to parental cells grown as adherent cultures.We report that epithelial markers E-cadherin and ZO-1 were downregulated,while mesenchymal markers Vimentin and Fibronectin were upregulated in 3-dimensional spheres.The 3-dimensional spheres also exhibited changes in expression of Snai,Zeb and Twist family of EMT transcription factors.CONCLUSION Our novel method successfully enriched stem-like cells which possessed an EMT phenotype.The isolation and characterization of murine hepatic CSCs could establish a precise target for the development of more effective therapies for HCC.

Calcium channel α2δ1 subunit as a novel biomarker for diagnosis of hepatocellular carcinoma

Objective:Hepatocellular carcinoma(HCC)is the fifth most common malignancy worldwide.The identification of new simple,inexpensive and highly accurate markers for HCC diagnosis and screening is needed.This case-control study evaluates the role of annexin A2 and voltage-gated calcium channelsα2δ1 subunit as serum biomarkers for HCC diagnosis.Methods:The study comprised three groups:group 1,50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection;group 2,25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC;and group 3,15 healthy controls.All participants were subjected to clinical and laboratory investigations,and radiological scanning.The serum levels of alpha-fetoprotein(AFP),annexin A2,and theα2δ1 subunit were evaluated by using ELISA technique.Results:The serum levels of annexin A2 significantly increased in patients with HCC(10.4±2.5 ng/m L;P<0.001)or with cirrhosis(9.31±1.8 ng/m L;P<0.001)comparing to that of healthy controls(0.296±0.09 ng/m L).However,there was no significant difference in serum annexin A2 levels in patients with HCC comparing to those with cirrhosis.Serumα2δ1 subunit significantly increased in patients with HCC(20.12±3.7 ng/m L)comparing to that in patients with cirrhosis(10.41±3.4 ng/m L,P<0.001)and healthy controls(10.2±2.9 ng/m L,P<0.001).Conclusions:The serumα2δ1 subunit may function as a new biomarker for HCC diagnosis.Conversely,serum annexin A2 has low diagnostic value as an HCC marker,especially in patients with underlying cirrhosis.

GhDET2,a Steroid 5alpha-reductase,Plays an Important Role in Cotton Fiber Cell Initiation and Elongation

Cotton(Gossypium hirsutum L.) fibers,one of the most important natural raw materials for the textile industry,are highly elongated trichomes from epidermal cells of cotton ovules.Among the longest plant cells ever characterized,cotton fiber is an ideal system for studying plant cell elongation.

A study of the initial adhesive force of cells on silk fibroin-based materials using micropipette aspiration

With the development of biomaterials,more attention is paid to the adhesion characteristics between cells and materials.It is necessary to study the adhesive force with a suitable method.Silk fibroin(SF)is widely investigated in biomedical application due to its novel biocompatibility and mechanical properties.In this article,the micropipette aspiration method and measurement pattern of uniform cells in round shape(UCR)was used to study the initial adhesive force of three types of cells on pure silk fibroin films(SFFs).We also compared the adhesive forces of modified SFFs with that of pure SFFs.The results of adhesive force in the initial adhesive stage were in concordance with the results of MTT assay andmicroscope observation,which were confirmed by the above three cell lines and four kinds of SFFs.The results indicated UCR was an efficient and quantitative measurement pattern in initial adhesion stage.This article also provides a useful method in identifying initial cell-materials interactions.