scholarly journals Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways

2006 ◽  
Vol 13 (2) ◽  
pp. 629-640 ◽  
Author(s):  
D Sharma ◽  
N K Saxena ◽  
P M Vertino ◽  
F A Anania
Keyword(s):  
Endometrial Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Weight Control ◽  
Cancer Growth ◽  
Obese Patients ◽  
Matrigel Invasion Assay ◽  
Direct Role ◽  
Matrigel Invasion ◽  
Risk Of Cancer

An increase in the risk of cancer is one of the consequences of obesity. The predominant cancers associated with obesity have a hormonal basis and include breast, prostate, endometrium, colon and gall-bladder cancers. Leptin, the key player in the regulation of energy balance and body weight control also acts as a growth factor on certain organs in both normal and disease states. Therefore, it is plausible that leptin acts to promote cancer growth by acting as a mitogenic agent. However, a direct role for leptin in endometrial cancer has not been demonstrated. In this study, we analyzed the proliferative role of leptin and the mechanism(s) underlying this action in endometrial cancers which express both short and long isoforms of leptin receptors. Treatment with leptin resulted in increased proliferation of ECC1 and Ishikawa cells. The promotion of endometrial cancer cell proliferation by leptin involves activation of STAT3 and ERK2 signaling pathways. Moreover, leptin-induced phosphorylation of ERK2 and AKT was dependent on JAK/STAT activation. Therefore blocking its action at the JAK/STAT level could be a rational therapeutic strategy for endometrial carcinoma in obese patients. We also found that leptin potently induces invasion of endometrial cancer cells in a Matrigel invasion assay. Leptin-stimulated invasion was effectively blocked by pharmacological inhibitors of JAK/STAT (AG490) and phosphatidylinositol 3-kinase (LY294002). Taken together these data indicate that leptin promotes endometrial cancer growth and invasiveness and implicate the JAK/STAT and AKT pathways as critical mediators of leptin action. Our findings have potential clinical implications for endometrial cancer progression in obese patients.

scholarly journals Nerves in the Tumor Microenvironment: Origin and Effects

2020 ◽  
Vol 8 ◽  
Author(s):  
Wenjun Wang ◽  
Lingyu Li ◽  
Naifei Chen ◽  
Chao Niu ◽  
Zhi Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Perineural Invasion ◽  
Vital Role ◽  
Cancer Growth ◽  
Alternative Route ◽  
Sympathetic Nervous ◽  
Molecular Bases

Studies have reported the vital role of nerves in tumorigenesis and cancer progression. Nerves infiltrate the tumor microenvironment thereby enhancing cancer growth and metastasis. Perineural invasion, a process by which cancer cells invade the surrounding nerves, provides an alternative route for metastasis and generation of tumor-related pain. Moreover, central and sympathetic nervous system dysfunctions and psychological stress-induced hormone network disorders may influence the malignant progression of cancer through multiple mechanisms. This reciprocal interaction between nerves and cancer cells provides novel insights into the cellular and molecular bases of tumorigenesis. In addition, they point to the potential utility of anti-neurogenic therapies. This review describes the evolving cross-talk between nerves and cancer cells, thus uncovers potential therapeutic targets for cancer.

scholarly journals Effect of microRNA-29b on proliferation, migration, and invasion of endometrial cancer cells

2019 ◽  
Vol 47 (8) ◽  
pp. 3803-3817
Author(s):  
Jian Kong ◽  
Xiuting He ◽  
Yan Wang ◽  
Jie Li
Keyword(s):  
Endometrial Cancer ◽  
Cancer Cells ◽  
Water Soluble ◽  
Migration And Invasion ◽  
Chemotherapy Response ◽  
Aberrant Expression ◽  
Altered Expression ◽  
Matrigel Invasion ◽  
Tensin Homolog ◽  
Induced Apoptosis

Objective Aberrant expression of microRNAs is a key regulator of tumorigenesis and progression in endometrial cancer. We assessed the effect of microRNA-29b (miR-29b) on proliferation, chemosensitivity, migration, and invasion of endometrial cancer cells. Methods The proliferation of endometrial cancer cells was examined by water-soluble tetrazolium (WST)-1 assay. The effects of miR-29b on migration and invasion were evaluated by transwell migration and Matrigel invasion assays. Western blotting was used to assess protein expression levels after altered expression of miR-29b. The effect of miR-29b on cisplatin-induced apoptosis was examined by Caspase-Glo 3/7 assay. Results miR-29b inhibited proliferation and decreased migration and invasion of endometrial cancer cells. It also enhanced the sensitivity of endometrial cancer cells to cisplatin and increased cisplatin-induced apoptosis by regulating expression of BAX and Bcl-2. Moreover, miR-29b changed the expression level of phosphatase and tensin homolog (PTEN) and p-AKT by directly binding to the 3′ untranslated region of PTEN. Conclusion miR-29b played important roles in proliferation and progression in endometrial cancer cells by direct regulation of PTEN. It might be used as a biomarker to predict chemotherapy response and prognosis in endometrial cancer.

Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells

2006 ◽  
Vol 387 (6) ◽  
pp. 807-811 ◽  
Author(s):  
Panagiotis Prezas ◽  
Matthias J.E. Arlt ◽  
Petar Viktorov ◽  
Antoninus Soosaipillai ◽  
Leon Holzscheiter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Vector Control ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Human Tissue ◽  
Control Cell ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Tissue Kallikrein ◽  
Matrigel Invasion

Abstract The human tissue kallikrein family of serine proteases (hK1–hK15 encoded by the genes KLK1–KLK15) is involved in several cancer-related processes. Accumulating evidence suggests that certain tissue kallikreins are part of an enzymatic cascade pathway that is activated in ovarian cancer and other malignant diseases. In the present study, OV-MZ-6 ovarian cancer cells were stably co-transfected with plasmids expressing hK4, hK5, hK6, and hK7. These cells displayed similar proliferative capacity as the vector-transfected control cells (which do not express any of the four tissue kallikreins), but showed significantly increased invasive behavior in an in vitro Matrigel invasion assay (p<0.01; Mann-Whitney U-test). For in vivo analysis, the cancer cells were inoculated into the peritoneum of nude mice. Simultaneous expression of hK4, hK5, hK6, and hK7 resulted in a remarkable 92% mean increase in tumor burden compared to the vector-control cell line. Five out of 14 mice in the ‘tissue kallikrein overexpressing’ group displayed a tumor/situs ratio greater than 0.198, while this weight limit was not exceeded at all in the vector control group consisting of 13 mice (p=0.017; χ2 test). Our results strongly support the view that tumor-associated overexpression of tissue kallikreins contributes to ovarian cancer progression.

scholarly journals Metabolic Reprogramming of Cancer Cells during Tumor Progression and Metastasis

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Kenji Ohshima ◽  
Eiichi Morii
Keyword(s):  
Oxidative Stress ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Treatment Strategies ◽  
Primary Site ◽  
Metabolic Reprogramming ◽  
Cancer Growth ◽  
Anchorage Independent Growth ◽  
Underlying Mechanisms

Cancer cells face various metabolic challenges during tumor progression, including growth in the nutrient-altered and oxygen-deficient microenvironment of the primary site, intravasation into vessels where anchorage-independent growth is required, and colonization of distant organs where the environment is distinct from that of the primary site. Thus, cancer cells must reprogram their metabolic state in every step of cancer progression. Metabolic reprogramming is now recognized as a hallmark of cancer cells and supports cancer growth. Elucidating the underlying mechanisms of metabolic reprogramming in cancer cells may help identifying cancer targets and treatment strategies. This review summarizes our current understanding of metabolic reprogramming during cancer progression and metastasis, including cancer cell adaptation to the tumor microenvironment, defense against oxidative stress during anchorage-independent growth in vessels, and metabolic reprogramming during metastasis.

scholarly journals Abnormal level of paxillin in cervical cancer cells is involved in tumor progression and invasion

2021 ◽  
Author(s):  
Hongqing Gu ◽  
Jing Wen
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Uterine Cervical Cancer ◽  
Cancer Growth ◽  
Over Expression ◽  
Apoptosis Inhibition ◽  
Cervical Cancer Cells ◽  
Elevated Expression ◽  
Abnormal Level

Human papillomavirus (HPV) is the primary causative agent for the uterine cervical cancer. The expression of oncoproteins E6/E7 promotes apoptosis inhibition and increases the risk of cervical cancer progression. Some research reported that elevated expression of paxillin (PXN) stimulated cancer growth and invasion. However, the clinical significance of PXN in cervical cancer has not been well characterized so far. We found that PXN mRNA expression and protein level are significantly upregulated in cervical cancer cells compared to adjacent normal cells. Furthermore, the paxillin over-expression was correlated with potential of tumorigenesis and invasion. Cervical cancer cells with increased paxillin expression had an ability to form more tumor clones and were characterized by higher invasiveness as well. Therefore, our findings suggest that paxillin may act as an important prognostic factor for cervical cancer patients as it promotes tumor regeneration and invasion.

scholarly journals Extract from the Coriolus versicolor Fungus as an Anti-Inflammatory Agent with Cytotoxic Properties against Endothelial Cells and Breast Cancer Cells

2020 ◽  
Vol 21 (23) ◽  
pp. 9063
Author(s):  
Tomasz Jędrzejewski ◽  
Justyna Sobocińska ◽  
Małgorzata Pawlikowska ◽  
Artur Dzialuk ◽  
Sylwia Wrotek
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Coriolus Versicolor ◽  
Bioactive Molecules ◽  
Ros Generation ◽  
Anti Inflammatory ◽  
Risk Of Cancer

Chronic inflammation is a well-recognised tumour-enabling component, which includes bioactive molecules from cells infiltrating the tumour microenvironment and increases the risk of cancer progression. Since long-term use of the currently available anti-inflammatory drugs used in cancer therapy causes numerous side effects, the aim of this study was to investigate the effect of an extract isolated from the Coriolus versicolor fungus (CV extract) on HUVEC endothelial cells and MCF-7 breast cancer cells in a pro-inflammatory microenvironment mimicked by lipopolysaccharide (LPS). The cells were simultaneously stimulated with the LPS and CV extract. After co-treatment, the cell viability, generation of reactive oxygen species (ROS), wound-healing assay, production of the pro-inflammatory and pro-angiogenic factors (interleukin (IL) 6, IL-8, and metalloproteinase (MMP) 9)), as well as expression of Toll-like receptor (TLR) 4 and phosphorylated IκB (p-IκB) were evaluated. The results showed that the CV extract inhibited IL-6, IL-8, and MMP-9 production by the LPS-stimulated cells. This effect was accompanied by a decrease in TLR4 and p-IκB expression. The CV extract also had anti-migratory properties and induced a cytotoxic effect on the cells that was enhanced in the presence of LPS. The observed cytotoxicity was associated with an increase in ROS generation. We conclude that the CV extract possesses cytotoxic activity against cancer cells and endothelial cells and has the ability to inhibit the expression of the pro-tumorigenic factors associated with inflammation.

scholarly journals Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Youn Kyung Choi ◽  
Sung-Gook Cho ◽  
Sang-Mi Woo ◽  
Yee Jin Yun ◽  
Sunju Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Herbal Extract ◽  
Tumor Growth And Metastasis ◽  
Risk Of Cancer

Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract fromAstragalus membranaceus, Angelica gigas, andTrichosanthes kirilowiiMaximowicz, suppressed MDA-MB-231 tumor growth and lung metastasisin vivoand reduced the viability and metastatic abilities of MDA-MB-231 cellsin vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path.

scholarly journals Carboxypeptidase E-∆N Promotes Proliferation and Invasion of Pancreatic Cancer Cells via Upregulation of CXCR2 Gene Expression

2019 ◽  
Vol 20 (22) ◽  
pp. 5725
Author(s):  
Sangeetha Hareendran ◽  
Xuyu Yang ◽  
Hong Lou ◽  
Lan Xiao ◽  
Y. Peng Loh
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Dependent Manner ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Carboxypeptidase E ◽  
Pancreatic Cancer Cells ◽  
Proliferation And Invasion

Pancreatic cancer is one of the leading causes of cancer-related mortality worldwide. The molecular basis for the pathogenesis of this disease remains elusive. In this study, we have investigated the role of wild-type Carboxypeptidase E (CPE-WT) and a 40 kDa N-terminal truncated isoform, CPE-ΔN in promoting proliferation and invasion of Panc-1 cells, a pancreatic cancer cell line. Both CPE-WT and CPE-ΔN were expressed in Panc-1 and BXPC-3 pancreatic cancer cells. Immunocytochemical studies revealed that in CPE transfected Panc-1 cells, CPE-ΔN was found primarily in the nucleus, whereas CPE-WT was present exclusively in the cytoplasm as puncta, characteristic of secretory vesicles. Endogenous CPE-WT was secreted into the media. Overexpression of CPE-ΔN in Panc-1 cells resulted in enhancement of proliferation and invasion of these cells, as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell proliferation assay and Matrigel invasion assay, respectively. In contrast, the expression of CPE-WT protein at comparable levels to CPE-ΔN in Panc-1 cells resulted in promotion of proliferation but not invasion. Importantly, there was an upregulation of the expression of CXCR2 mRNA and protein in Panc-1 cells overexpressing CPE-ΔN, and these cells exhibited significant increase in proliferation in a CXCR2-dependent manner. Thus, CPE-ΔN may play an important role in promoting pancreatic cancer growth and malignancy through upregulating the expression of the metastasis-related gene, CXCR2.

scholarly journals Assessment of Antitumor Activity of Vinca herbacea on Human Ovarian Cancer Cell Line

2021 ◽  
Vol 3 (2) ◽  
pp. 115-126
Author(s):  
Somayeh Dehghanipour ◽  
◽  
Sara Saadatmand ◽  
Nasim Hayati Roodbari ◽  
Mehdi Mahdavi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Dependent Manner ◽  
Matrigel Invasion Assay ◽  
Matrigel Invasion ◽  
Skov3 Cells

Background: It seems that Vinca. herbacea has an anti-tumor effect. Here, the immunotherapeutic effect of this compound is assessed against human ovarian cancer (SKOV3) cells because of the high incidence of this tumor in women. Materials and Methods: The cytotoxic activity of V. herbacea extract against human ovarian cancer (SKOV3) cells was determined by MTT assay. The apoptosis-inducing potential of V. herbacea extract was investigated using the FITC-V Annexin kit. The Matrigel invasion assay was used to investigate the ability of V. herbacea extract in reducing ovarian cancer cells invasion. Real-time PCR using specific primers was performed to investigate the expression of angiogenesis (VEGFR1, VEGFR2, and VEGF-A), apoptosis (Bcl-2 and Bax), and metastasis (MMP2 and MMP9) genes. Results: V. herbacea caused a significant cytotoxic effect against human ovarian cancer cells in a dose-dependent manner. V. herbacea induced apoptosis in SKOV3 cells through caspase-3 activation and an increase in the expression ratio of Bax/Bcl-2. V. herbacea inhibited cancer cells’ angiogenesis, which was evident by the significant reduction in the expression of angiogenesis-related genes, including VEGF, VEGFR-1, and VEGFR-2. Besides, V. herbacea inhibited cancer cell adhesion and invasion. Conclusion: V. herbacea extract elicits a robust cytostatic effect in SKOV3 cells by modulating the activity and or the expression of proteins regulating the process of cellular apoptosis, adhesion invasion, and angiogenesis.

scholarly journals Quantifying the Morphology and Mechanisms of Cancer Progression in 3D in-vitro environments: Integrating Experiments, Multiscale Models, and Spatial Validation

2021 ◽  
Author(s):  
Nikolaos M Dimitriou ◽  
Salvador Flores-Torres ◽  
Joseph Matthew Kinsella ◽  
Georgios D Mitsis
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Quantitative Description ◽  
Morphological Characteristics ◽  
Random Motion ◽  
Cancer Growth ◽  
Chemotactic Migration ◽  
Wide Range ◽  
3D Environments

Throughout the years, mathematical models of cancer growth have become increasingly more accurate in terms of the description of cancer growth in both space and time. However, the limited amount of data typically available has resulted in a larger number of qualitative rather than quantitative studies. In this study, we provide an integrated experimental-computational framework for the quantification of the morphological characteristics and the mechanistic modelling of cancer progression in 3D environments. The proposed framework allows the calibration of multiscale-spatiotemporal models of cancer growth using 3D cell culture data, and their validation based on the morphological patterns. The implementation of this framework enables us to pursue two goals; first, the quantitative description of the morphology of cancer progression in 3D cultures, and second, the relation of tumour morphology with underlying biophysical mechanisms that govern cancer growth. We apply this framework to the study of the spatiotemporal progression of Triple Negative Breast Cancer (TNBC) cells cultured in 3D Matrigel scaffolds, under the hypothesis of chemotactic migration using a multiscale Keller-Segel model. The results reveal transient, non-random spatial distributions of cancer cells that consist of clustered patterns across a wide range of neighbourhood distances, as well as dispersion for larger distances. Overall, the proposed model was able to describe the general characteristics of the experimental observations and suggests that cancer cells exhibited chemotactic migration and cell accumulation, as well as random motion throughout the period of development. To our knowledge, this is the first time a framework attempts to quantify the relationship of the spatial patterns and the underlying mechanisms of cancer growth in 3D environments.

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