scholarly journals The LIN28B/TGF-β/TGFBI feedback loop promotes cell migration and tumour initiation potential in cholangiocarcinoma

2021 ◽  
Author(s):  
Nattapong Puthdee ◽  
Sira Sriswasdi ◽  
Trairak Pisitkun ◽  
Sutheera Ratanasirintrawoot ◽  
Nipan Israsena ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Migration ◽  
Feedback Loop ◽  
Rna Binding ◽  
Primary Liver Cancer ◽  
High Rate ◽  
Type I ◽  
Spheroid Formation ◽  
Mesenchymal Transition ◽  
Cholangiocarcinoma Cell

AbstractCholangiocarcinoma (CCA), a lethal malignancy of the biliary epithelium, is the second most common primary liver cancer. The poor prognosis of CCA is due to the high rate of tumour invasion and distant metastasis. We found that the RNA-binding protein LIN28B, a known regulator of microRNA biogenesis, stem cell maintenance, and oncogenesis, is expressed in a subpopulation of CCA patients. To further investigate the potential role of LIN28B in CCA pathogenesis, we studied the effect of LIN28B overexpression in the cholangiocyte cell line MMNK-1 and cholangiocarcinoma cell lines HuCCT-1 and KKU-214. Here, we show that enhanced LIN28B expression promoted cancer stem cell-like properties in CCA, including enhanced cell migration, epithelial-to-mesenchymal transition (EMT), increased cell proliferation and spheroid formation. Proteomic analysis revealed TGF-β-induced protein (TGFBI) as a novel LIN28B target gene, and further analysis showed upregulation of other components of the TGF-β signalling pathway, including TGF-β receptor type I (TGFBRI) expression and cytokine TGFB-I, II and III secretion. Importantly, the small molecule TGF-β inhibitor SB431542 negated the effects of LIN28B on both cell migration and clonogenic potential. Overexpression of TGFBI alone promoted cholangiocarcinoma cell migration and EMT changes, but not spheroid formation, suggesting that TGFBI partially contributes to LIN28B-mediated aggressive cell behaviour. These observations are consistent with a model in which TGF-β and LIN28B work together to form a positive feedback loop during cholangiocarcinoma metastasis and provide a therapeutic intervention opportunity.

scholarly journals Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes

Marine Drugs ◽  
2019 ◽  
Vol 17 (7) ◽  
pp. 424
Author(s):  
Sajee Thaweekitphathanaphakdee ◽  
Pithi Chanvorachote ◽  
Sagaw Prateepchinda ◽  
Mattaka Khongkow ◽  
Apirada Sucontphunt
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Stem Cell ◽  
Cell Migration ◽  
Expression Level ◽  
Epidermal Keratinocytes ◽  
Stem Cell Markers ◽  
Spheroid Formation ◽  
Human Epidermal Keratinocytes ◽  
Cell Markers

Stem cell activities in human tissues are critical for tissue integrity and function. Maintaining keratinocyte stem cells (KSCs) stemness helps sustain healthy skin by supporting keratinocyte renewal, involving the formation of epidermal barriers. In this study, abalone collagen (AC) extracts with molecular weights of 3 kDa (AC 1) and 300 kDa (AC 2) were compared to the epidermal growth factor (EGF) for their effects on cell proliferation, cell migration (wound healing), spheroid formation, and the expression level of stem cell markers on human keratinocytes (HaCaT cells). Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell proliferation was quantified by ATP and DNA content analysis and Sulforhodamine B (SRB) assays. Cell migration assay was determined using the scratch wound healing test. Spheroid formation was evaluated and the expression level of stem cell markers was investigated by western blot analysis. The results showed that AC 1 at the concentration of 100 µg/mL could stimulate HaCaT cell proliferation, migration, spheroid formation, and the expression level of stem cell markers (keratin 19, β-catenin, ALDH1A1) compared to the control. In conclusion, a smaller molecular weight of abalone collagen extract exhibits a better effect on keratinocytes proliferation, migration, and stemness, which could be a potential active ingredient in cosmeceutical products.

scholarly journals Curcumin inhibits breast cancer stem cell migration by amplifying the E-cadherin/β-catenin negative feedback loop

2014 ◽  
Vol 5 (5) ◽  
pp. 116 ◽  
Author(s):  
Shravanti Mukherjee ◽  
Minakshi Mazumdar ◽  
Samik Chakraborty ◽  
Argha Manna ◽  
Shilpi Saha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cell Migration ◽  
Cancer Stem Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Breast Cancer Stem Cell ◽  
Negative Feedback Loop ◽  
Stem Cell Migration ◽  
E Cadherin

scholarly journals Acidic microenvironment modulates ROR1 to promote epithelial-mesenchymal transition and hepatocarcinoma metastasis

2021 ◽  
pp. jcs.255349
Author(s):  
Xia Meng ◽  
Yurui Xu ◽  
Xinghai Ning
Keyword(s):  
Cell Migration ◽  
Tyrosine Kinases ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Potential ◽  
Orphan Receptor ◽  
High Rate ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Acidic Microenvironment

The tendency of metastasis in hepatocarcinoma results in a high rate of mortality, making it a hot research topic in cancer studies. Although tumor acidic microenvironment has been proved to promote cancer metastasis, its underlying regulatory mechanisms remain poorly defined. Here, we found that acidic conditions significantly enhanced cell migration and invasion ability in hepatocellular carcinoma, and the expression of receptor tyrosine kinases-like orphan receptor 1 (ROR1) was distinctly upregulated in acid-treated cells. In addition, siRNA knockdown of ROR1 could effectively inhibit acid-induced cell migration, invasion and epithelial-mesenchymal transition (EMT). Importantly, neutralization of acidic environment with NaHCO3 could downregulate acid-stimulated ROR1 expression, thereby retarding cell metastatic potential. Especially, the formation of metastatic nodules was significantly increased after intrapulmonary injection of acid stimulated cancer cells, which were inhibited by pretreating with NaHCO3. In summary, we reveal that tumor acidic microenvironment modulates ROR1 expression to promote tumor metastasis, which provides not only a better understanding of molecular mechanism related to metastasis, but a promising target for tumor management.

Study on Functional Monoclonal Antibodies of Anti-Human Uterine Sarcoma Stem Cell-Like CellsStudy on Functional Monoclonal Antibodies of Anti-Human Uterine Sarcoma Stem Cell-Like Cells

2020 ◽  
Author(s):  
Jiuping Gao ◽  
Beilei Zhang ◽  
Dihong Tang ◽  
Ting Gao ◽  
Qiuhui Lin ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Stem Cell ◽  
Cell Migration ◽  
Cell Line ◽  
Colony Formation ◽  
Formation Rate ◽  
Uterine Sarcoma ◽  
Dependent Manner ◽  
Spheroid Formation

Abstract Background: To establish a functional monoclonal antibody library using Human Uterine Sarcoma Stem Cell-Like Cells (HUSSLCs) to screen and identify functional monoclonal antibodies that can recognize and inhibit HUSSLCs.Methods: B lymphocytes in proliferative state were prepared by using the second generation CD133+spheroid cells of SK-UT-1 cell line, i.e. HUSSLCs, as antigens; Spheroid formation, agar colony formation, wound healing, flow cytometry, and Western blotting were adopted to detect the effect of monoclonal antibodies with varied dilution ratios on HUSSLCs spheroid formation, agar colony formation, cell migration, CD133 expression, and expression of CD44, ABCG2, Bmi1, Nanog, Oct4 and ALDH1.Results: Myeloma cells of SP2/0 cell line can achieve 85% degrees of fusion and results of 1-2F monoclonal cell supernatants with different dilution ratios reduced HUSSLCs spheroid formation rate, agar colony formation rate, cell migration rate, CD133 positive cell expression and protein expression levels of CD44, ABCG2, Bmi1, Nanog, Oct4, and ALDH1 in concentration-dependent manner (P <0.05).Conclusion: The antibody valence produced by HUSSLCs-immunized mice reached the requirement for preparation of monoclonal antibody. Anti-HUSSLCs monoclonal antibodies feature functions of inhibiting the self-renewal, unrestricted proliferation, migration, invasion and multidrug resistance of HUSSLCs and functions characterized by tumor stem cells.

Comparisons of Growth Features and Cancer Stem Cell Prevalences in Intrahepatic and Extrahepatic Cholangiocarcinoma Cell Lines

2021 ◽  
Author(s):  
Jiaqi Yang ◽  
David P Sontag ◽  
Frank Burczynski ◽  
Shengyan Xi ◽  
Yuewen Gong ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tumor Cell ◽  
Cell Lines ◽  
Expression Profiles ◽  
Migration And Invasion ◽  
Spheroid Formation ◽  
Extrahepatic Cholangiocarcinoma ◽  
Cholangiocarcinoma Cell ◽  
And Migration ◽  
Growth Features

Abstract Background: Intra- and extra- hepatic cholangiocarcinoma (I-CCA and E-CCA respectively) exhibit different growth features that contribute to different clinical outcomes. Cancer stem cells (CSCs) influence tumor growth and thereby, may be responsible for these differences. The aim of this study was to document and compare the growth features of human I-CCA and E-CCA cell lines and determine whether any differences observed could be explained by differences in the prevalence and/or stem cell surface marker (SCSM) expression profiles of CSCs within the tumor cell lines. Methods: Six CCA cells lines, three I-CCA and three E-CCA, were studied. Tumor cell growth features including cell proliferation, colony/spheroid formation, migration and invasion were documented. CSC prevalence and SCSM expression profiles were examined by flow cytometry. Results: I-CCA cells had significantly increased proliferative activity, shorter doubling times and were more invasive than E-CCA cells, while colony/spheroid formation and migration were similar in the two cell populations. There were no significant differences in CSC prevalences and/or SCSM expression profiles. Conclusion: These findings suggest that I-CCA cells proliferate at a more rapid rate and are more invasive than E-CCA cells but the differences cannot be explained by differences in the prevalence or SCSM expression profiles of CSCs within the tumor cell population.

scholarly journals Breast Cancer Classification Based on Tumor Budding and Stem Cell-Related Signatures Facilitate Prognosis Evaluation

2022 ◽  
Vol 11 ◽  
Author(s):  
Zhenxian Xiang ◽  
Qiuming He ◽  
Li Huang ◽  
Bin Xiong ◽  
Qingming Xiang
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Tumor Budding ◽  
Categorical Variables ◽  
Type I ◽  
High Grade ◽  
Mesenchymal Transition ◽  
Node Metastasis ◽  
Type Iv

BackgroundTumor budding (TB) is emerging as a prognostic factor in multiple cancers. Likewise, the stemness of cancer cells also plays a vital role in cancer progression. However, nearly no research has focused on the interaction of TB and tumor stemness in cancer.MethodsTissue microarrays including 229 cases of invasive breast cancer (BC) were established and subjected to pan-cytokeratin immunohistochemical staining to evaluate molecular expression. Univariate and multivariate analyses were applied to identify prognostic factors of BC, and the Chi-square test was used for comparison of categorical variables.ResultsHigh-grade TB was significantly associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, epithelial-mesenchymal transition, and poor disease-free survival (DFS) of BC patients. We also found that the prognostic value of TB varied widely among different subtypes and subgroups. Cox regression analysis then showed that TB grade was an independent prognostic factor. Moreover, cancer stem cell (CSC) markers CD44 and ALDH1A1 were significantly higher in high-grade TB tumors. Consequently, patients were classified into high CSC score subgroup and low CSC score subgroups. Further research found that CSC scores correlated with clinicopathological features and DFS of BC patients. Based on TB grade and CSC scores, we classified BC patients into TBlow-CSCslow (type I), TBlow-CSCshigh (type II), TBhigh-CSCslow (type III), and TBhigh-CSCshigh (type IV) subgroups. Survival analysis showed that patients in the type I subgroup had the best DFS, whereas those in the type IV subgroup had the worst DFS. Finally, a TB-CSC-based nomogram for use in BC was established. The nomogram was well calibrated to predict the probability of 5-year DFS, and the C-index was 0.837. Finally, the area under the curve value for the nomogram (0.892) was higher than that of the TNM staging system (0.713).ConclusionThe combination of TB grade with CSC score improves the prognostic evaluation of BC patients. A novel nomogram containing TB grade and CSC score provides doctors with a candidate tool to guide the individualized treatment of cancer patients.

scholarly journals Pancreatic Lineage Specifier PDX1 Increases Adhesion and Decreases Motility of Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4390
Author(s):  
Liya Kondratyeva ◽  
Igor Chernov ◽  
Eugene Kopantzev ◽  
Dmitry Didych ◽  
Alexey Kuzmich ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Motility ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Type I ◽  
Mesenchymal Transition ◽  
Tumor Cell Migration

Intercellular interactions involving adhesion factors are key operators in cancer progression. In particular, these factors are responsible for facilitating cell migration and metastasis. Strengthening of adhesion between tumor cells and surrounding cells or extracellular matrix (ECM), may provide a way to inhibit tumor cell migration. Recently, we demonstrated that PDX1 ectopic expression results in the reduction of pancreatic cancer line PANC-1 cell motility in vitro and in vivo, and we now provide experimental data confirming the hypothesis that suppression of migration may be related to the effect of PDX1 on cell adhesion. Cell migration analyses demonstrated decreased motility of pancreatic Colo357 and PANC-1 cell lines expressing PDX1. We observed decreased expression levels of genes associated with promoting cell migration and increased expression of genes negatively affecting cell motility. Expression of the EMT regulator genes was only mildly induced in cells expressing PDX1 during the simulation of the epithelial-mesenchymal transition (EMT) by the addition of TGFβ1 to the medium. PDX1-expressing cancer cell lines showed increased cell adhesion to collagen type I, fibronectin, and poly-lysine. We conclude that ectopic expression of PDX1 reduces the migration potential of cancer cells, by increasing the adhesive properties of cells and reducing the sensitivity to TGFβ1-induced EMT.

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