1.Epigallocatechin-3-gallate inhibits paracrine and autocrine hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion.
In hae KWAK ; Yun Hye SHIN ; Myeongdeok KIM ; Hyun Young CHA ; Hyun Ja NAM ; Bok Soon LEE ; S C CHAUDHARY ; Ki Soo PAI ; Jae Ho LEE
Experimental & Molecular Medicine 2011;43(2):111-120
Aberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the cell-based screening assay, (-)epigallocatechin-3-gallate (EGCG) inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering and uPA activation (IC50 = 15.8 microg/ml). Further analysis revealed that EGCG at low doses specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met but not epidermal growth factor (EGF)-induced phosphorylation of EGF receptor (EGFR). On the other hand, high-dose EGCG decreased both Met and EGFR proteins. We also found that EGCG did not act on the intracellular portion of Met receptor tyrosine kinase, i.e., it inhibited InlB-dependent activation of Met but not NGF-induced activation of Trk-Met hybrid receptor. This inhibition decreased HGF-induced migration and invasion by parental or HGF/SF-transfected B16F10 melanoma cells in vitro in either a paracrine or autocrine manner. Furthermore, EGCG inhibited the invasion/metastasis of HGF/SF-transfected B16F10 melanoma cells in mice. Our data suggest the possible use of EGCG in human cancers associated with dysregulated paracrine or autocrine HGF/SF-Met signaling.
Animals
;
Autocrine Communication/*drug effects
;
Catechin/*analogs & derivatives/metabolism/pharmacology
;
Cell Line, Tumor
;
Cell Movement/drug effects
;
Female
;
*Hepatocyte Growth Factor
;
Humans
;
Mice
;
Mice, Inbred BALB C
;
Neoplasms, Experimental/*metabolism/pathology
;
Paracrine Communication/*drug effects
;
Phosphorylation/drug effects
;
Proto-Oncogene Proteins c-met/antagonists & inhibitors/metabolism
;
Receptors, Growth Factor/antagonists & inhibitors/metabolism
;
Signal Transduction
2.Expression and Clinical Significance of Angiopoietin-2 and its Receptor Tie-2 in Invasive Breast Cancer.
Journal of Korean Breast Cancer Society 2004;7(2):84-91
PURPOSE: Breast carcinomas are highly malignant tumor that the angiogenesis factor, vascular endothelial growth factor and its receptors are overexpressed. To elucidate the role of Angiopoietin-2 (ANG2) and ANG2 receptor Tie-2 in invasive ductal carcinoma, we examined the expression of ANG2, and Tie-2 at the mRNA and protein levels in human breast cancer cell lines and samples. METHODS: Total RNA from 22 breast cancer patient biopsies were extracted. ANG2 and Tie-2 mRNA expression was measured by means of reverse transcription-PCR assay. RESULTS: RT-PCR indicated that the ANG2 and Tie-2 mRNA levels in carcinoma samples were significantly higher than those of the adjacent non-neoplastic breast tissues. For ANG2 and Tie-2, 41 of 71 invasive ductal carcinomass (58%) showed high expressions in Immunohistochemistry. Immunohistochemical analysis demonstrated that ANG2 and Tie-2 were expressed by both tumor cells and endothelial elements. Expression in tumor cells were confirmed by studying a panel of human breast carcinoma cell lines cultured by RT-PCR. Our study showed that the ANG2 positivity was correlated with axillary lymph node metastasis among the clinicopathological parameter and confirmed that high expressions of ANG2 correlated highly with the axillary lymph node metastases, histological grade, positive PR status, and age, and Tie-2 expression correlated significantly with the p53 status. Moreover, ANG2 and Tie-2 co-expression correlated significantly with the axillary lymph node metastases, compared with ANG2(-)/Tie-2 (-) and ANG2 (+)/Tie-2 (-) or ANG2 (-)/Tie-2 (+) cases. CONCLUSION: These findings suggested that ANG2 and Tie-2 might be involved in the progression of invasive ductal carcinomas through autocrine and paracrine signaling and that it may be clinically useful in selecting patients who could benefit from adjuvant treatment by further study.
Angiogenesis Inducing Agents
;
Angiopoietin-2*
;
Biopsy
;
Breast Neoplasms*
;
Breast*
;
Carcinoma, Ductal
;
Cell Line
;
Humans
;
Immunohistochemistry
;
Lymph Nodes
;
Neoplasm Metastasis
;
Paracrine Communication
;
RNA
;
RNA, Messenger
;
Vascular Endothelial Growth Factor A
3.Research progresses of paracrine effect of bone marrow derived mesenchymal stem cells on wound healing.
Qing LUO ; Chen ZHANG ; Guanbin SONG
Journal of Biomedical Engineering 2012;29(5):999-1002
Bone marrow derived mesenchymal stem cell (BMSC) is one of the crucial cell types which plays roles in wound healing of tissues. In the last decades, it was believed that BMSCs promoted wound healing by differentiating into multiple lineages and placing the wounded tissues. In recent years, a new viewpoint arose from evidences that the paracrine effect of BMSCs might play a more important role in the process of wound healing than differentiation. Understanding the role of BMSCs paracrine in wound healing would be vital to clarify the mechanism how BMSCs take part into the process of wound healing. In this paper, we review the new research processes of BMSCs paracrine in wound healing of tissues.
Animals
;
Bone Marrow Cells
;
cytology
;
physiology
;
Cell Differentiation
;
physiology
;
Cells, Cultured
;
Humans
;
Mesenchymal Stromal Cells
;
cytology
;
physiology
;
Paracrine Communication
;
physiology
;
Wound Healing
;
physiology
4.Effect of Hypoxic Paracrine Media on Calcium-Regulatory Proteins in Infarcted Rat Myocardium.
Byeong Wook SONG ; Hye Jin HWANG ; Minji SEUNG ; Moon Hyoung LEE
Korean Circulation Journal 2014;44(1):16-21
BACKGROUND AND OBJECTIVES: An increase in intracellular calcium concentration due to loss of Ca2+ homeostasis triggers arrhythmia or cardiac cell death in the heart. Paracrine factors released from stem cells have beneficial cardioprotective effects. However, the mechanism of modulation of Ca2+ homeostasis by paracrine factors in ischemic myocardium remains unclear. MATERIALS AND METHODS: We isolated rat bone marrow-derived mesenchymal stem cells (MSCs), and prepared paracrine media (PM) from MSCs under hypoxic or normoxic conditions (hypoxic PM and normoxic PM). We induced rat myocardial infarction by left anterior descending ligation for 1 hour, and treated PM into the border region of infarcted myocardium (n=6/group) to identify the alteration in calcium-regulated proteins. We isolated and stained the heart tissue with specific calcium-related antibodies after 11 days. RESULTS: The hypoxic PM treatment increased Ca2+-related proteins such as L-type Ca2+ channel, sarcoplasmic reticulum Ca2+ ATPase, Na+/K+ ATPase, and calmodulin, whereas the normoxic PM treatment increased those proteins only slightly. The sodium-calcium exchanger was significantly reduced by hypoxic PM treatment, compared to moderate suppression by the normoxic PM treatment. CONCLUSION: Our results suggest that hypoxic PM was significantly associated with the positive regulation of Ca2+ homeostasis in infarcted myocardium.
Adenosine Triphosphatases
;
Animals
;
Antibodies
;
Arrhythmias, Cardiac
;
Calcium
;
Calcium-Transporting ATPases
;
Calmodulin
;
Cell Death
;
Heart
;
Homeostasis
;
Ligation
;
Mesenchymal Stromal Cells
;
Myocardial Infarction
;
Myocardium*
;
Paracrine Communication
;
Rats*
;
Sarcoplasmic Reticulum
;
Sodium-Calcium Exchanger
;
Stem Cells
5.Initiation of human parturition: signaling from senescent fetal tissues via extracellular vesicle mediated paracrine mechanism
Obstetrics & Gynecology Science 2019;62(4):199-211
A better understanding of the underlying mechanisms by which signals from the fetus initiate human parturition is required. Our recent findings support the core hypothesis that oxidative stress (OS) and cellular senescence of the fetal membranes (amnion and chorion) trigger human parturition. Fetal membrane cell senescence at term is a natural physiological response to OS that occurs as a result of increased metabolic demands by the maturing fetus. Fetal membrane senescence is affected by the activation of the p38 mitogen activated kinase-mediated pathway. Similarly, various risk factors of preterm labor and premature rupture of the membranes also cause OS-induced senescence. Data suggest that fetal cell senescence causes inflammatory senescence-associated secretory phenotype (SASP) release. Besides SASP, high mobility group box 1 and cell-free fetal telomere fragments translocate from the nucleus to the cytosol in senescent cells, where they represent damage-associated molecular pattern markers (DAMPs). In fetal membranes, both SASPs and DAMPs augment fetal cell senescence and an associated ‘sterile’ inflammatory reaction. In senescent cells, DAMPs are encapsulated in extracellular vesicles, specifically exosomes, which are 30–150 nm particles, and propagated to distant sites. Exosomes traffic from the fetus to the maternal side and cause labor-associated inflammatory changes in maternal uterine tissues. Thus, fetal membrane senescence and the inflammation generated from this process functions as a paracrine signaling system during parturition. A better understanding of the premature activation of these signals can provide insights into the mechanisms by which fetal signals initiate preterm parturition.
Aging
;
Cell Aging
;
Cytosol
;
Exosomes
;
Extracellular Vesicles
;
Extraembryonic Membranes
;
Female
;
Fetus
;
Humans
;
Inflammation
;
Membranes
;
Obstetric Labor, Premature
;
Oxidative Stress
;
Paracrine Communication
;
Parturition
;
Phenotype
;
Pregnancy
;
Premature Birth
;
Risk Factors
;
Rupture
;
Telomere
6.Autocrine effect of vascular endothelial growth factor on the proliferation of HaCaT cells.
Xiao-hong YANG ; Xiao-yong MAN ; Sui-qing CAI ; Chun-ming LI ; Jiong ZHOU ; Min ZHENG
Journal of Zhejiang University. Medical sciences 2009;38(4):338-342
OBJECTIVETo determine the autocrine effect of vascular endothelial growth factor (VEGF) on epidermal keratinocytes HaCaT cells.
METHODSCultured HaCaT cells were treated with various concentrations of VEGF(165) (0,1,5,10,25,50,100 ng/ml) or Avastin (0,0.063,0.125,0.25,0.50,1.0,2.0 mg/ml) in vitro. HaCaT cell proliferation was determined by MTT assay and the cell migration was measured by migration assay. The effect of VEGF(165) (10 ng/ml) on phosphorylation of ERK1/2 was detected in HaCaT cells pretreated or not pretreated with Avastin (0.5 mg/ml).
RESULTSVEGF enhanced the proliferation and migration of HaCaT cells in a dose-dependent manner, while Avastin inhibited the effects of VEGF also in a dose-dependent manner. VEGF(165) (10 ng/ml) induced the phosphorylation of ERK1/2 in HaCaT cells,but which was blocked by Avastin (0.5 mg/ml).
CONCLUSIONVEGF enhanced the proliferation and migration of HaCaT cells in a dose-dependent manner, while Avastin inhibited the effects of VEGF also in a dose-dependent manner. VEGF(165) (10 ng/ml) induced the phosphorylation of ERK1/2 in HaCaT cells,but which was blocked by Avastin (0.5 mg/ml).
Autocrine Communication ; Cell Line ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Epidermis ; cytology ; Humans ; Keratinocytes ; cytology ; Skin ; cytology ; Vascular Endothelial Growth Factor A ; pharmacology
7.New avenues for systematically inferring cell-cell communication: through single-cell transcriptomics data.
Xin SHAO ; Xiaoyan LU ; Jie LIAO ; Huajun CHEN ; Xiaohui FAN
Protein & Cell 2020;11(12):866-880
For multicellular organisms, cell-cell communication is essential to numerous biological processes. Drawing upon the latest development of single-cell RNA-sequencing (scRNA-seq), high-resolution transcriptomic data have deepened our understanding of cellular phenotype heterogeneity and composition of complex tissues, which enables systematic cell-cell communication studies at a single-cell level. We first summarize a common workflow of cell-cell communication study using scRNA-seq data, which often includes data preparation, construction of communication networks, and result validation. Two common strategies taken to uncover cell-cell communications are reviewed, e.g., physically vicinal structure-based and ligand-receptor interaction-based one. To conclude, challenges and current applications of cell-cell communication studies at a single-cell resolution are discussed in details and future perspectives are proposed.
Animals
;
Cell Communication
;
Humans
;
RNA-Seq
;
Single-Cell Analysis
;
Transcriptome
8.Exosomes Derived from Mesenchymal Stem Cells--the Future Ideal Vector of Biological Therapy.
Juan ZHANG ; Jing-Shu SHI ; Jian LI
Journal of Experimental Hematology 2015;23(4):1179-1183
MSC-exosomes are homogeneous menbrane vesicles with diameter 40-100 nm, derived from mesenchymal stem cells at physiological or pathology conditions. MSC-exosomes contain a great quantity and a wide variety of bioactive substances, such as proteins and miRNA. MSC-exosomes transfer bioactive substances to recipient cells to affect their functions through membrane fusion or endocytosis, which like the storage pools of signal vehicles for cell-to-cell comunication in vivo. MSC-exosomes can mimic the beneficial effect of MSC treatment, such as the promotion of tissue repair or the immune regulation. The biological property and functions of MSC-exosomes are reviwed in this article.
Biological Therapy
;
Cell Communication
;
Exosomes
;
Humans
;
Mesenchymal Stromal Cells
;
MicroRNAs
9.Role of Exosome Shuttle RNA in Cell-to-Cell Communication.
Wei ZHANG ; Peng PENG ; Keng SHEN
Acta Academiae Medicinae Sinicae 2016;38(4):480-483
There are several ways that transpire in cell-to-cell communication,with or without cell contact. Exosomes play an important role in cell-to-cell communication,which do not need cell contact,as that can result in a relatively long-distance influence. Exosome contains RNA components including mRNA and micro-RNA,which are protected by exosomes rigid membranes. This allows those components be passed long distance through the circulatory system. The mRNA components are far different from their donor cells,and the micro-RNA components may reflect the cell they originated. In this article we review the role of exosomes in cell-to-cell communication,with particular focus on their potentials in both diagnostic and therapeutic applications.
Cell Communication
;
Exosomes
;
Humans
;
MicroRNAs
;
genetics
;
RNA, Messenger
;
genetics
10.Advances in the Urinary Exosomes in Renal Diseases.
Pei-Pei CHEN ; Yan QIN ; Xue-Mei LI
Acta Academiae Medicinae Sinicae 2016;38(4):464-469
Cells secrete around 30- 100 nm membrane-enclosed vesicles that are released into the extracellular spaceis termed exosomes(EXs). EXs widely present in body fluids and incorporated proteins,nucleic acids that reflect the physiological state of their cells of origin and they may play an important role in cell-to-cell communication in various physiological and disease processes. In this article we review the recent basic and clinical studies in urinary EXs in renal diseases,focusing on their biological characteristics and potential roles as new biological markers,intervention treatment goals,and targeted therapy vectors in renal diseases.However,some issues still exist;in particular,the clinical application of EXs as a liquid biopsy technique warrants further investigations.
Biomarkers
;
urine
;
Cell Communication
;
Exosomes
;
Humans
;
Kidney Diseases
;
diagnosis