scholarly journals Inverse Reconstruction of Cell Proliferation Laws in Cancer Invasion Modelling

2021 ◽  
Author(s):  
Dumitru Trucu ◽  
Maher Alwuthaynani
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Deep Understanding ◽  
Problem Formulation ◽  
Cancer Invasion ◽  
Surrounding Tissue ◽  
Inverse Reconstruction ◽  
Modelling Studies ◽  
Cancer Modelling

The process of local cancer cell invasion of the surrounding tissue is key for the overall tumour growth and spread within the human body, the past 3 decades witnessing intense mathematical modelling efforts in these regards. However, for a deep understanding of the cancer invasion process these modelling studies require robust data assimilation approaches. While being of crucial importance in assimilating potential clinical data, the inverse problems approaches in cancer modelling are still in their early stages, with questions regarding the retrieval of the characteristics of tumour cells motility, cells mutations, and cells population proliferation, remaining widely open. This study deals with the identification and reconstruction of the usually unknown cancer cell proliferation law in cancer modelling from macroscopic tumour snapshot data collected at some later stage in the tumour evolution. Considering two basic tumour configurations, associated with the case of one cancer cells population and two cancer cells subpopulations that exercise their dynamics within the extracellular matrix, we combine Tikhonov regularisation and gaussian mollification approaches with finite element and finite differences approximations to reconstruct the proliferation laws for each of these sub-populations from both exact and noisy measurements. Our inverse problem formulation is accompanied by numerical examples for the reconstruction of several proliferation laws used in cancer growth modelling.

scholarly journals Colorectal Cancer Invasion and Atrophy of the Enteric Nervous System: Potential Feedback and Impact on Cancer Progression

2020 ◽  
Vol 21 (9) ◽  
pp. 3391
Author(s):  
Janusz Godlewski ◽  
Zbigniew Kmiec
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Invasion ◽  
Signalling Pathways ◽  
Cancer Cell Proliferation ◽  
Nerve Fibres

Colorectal cancer (CRC) invasion within the large intestine wall results in the replacement of normal tissue architecture by tumour mass. Cancer cells digest the extracellular matrix (ECM) by the release of proteolytic enzymes. The disintegration of matrix ground substance activates several deposited growth factors which stimulate cell proliferation. Stromal (mainly fibroblasts), immune and cancer cells dominate in this area and become involved in a network of multimodal interactions which significantly induce proliferation of colon cancer cells, inhibit their apoptosis and promote their spreading within the local tumour microenvironment. Cancer invasion destroys nerve fibres and neurons of the local enteric nervous system (ENS) and induces subsequent atrophy of the submucosal and myenteric plexuses in areas adjacent to the cancer boundary. Interestingly, the reduction of plexuses’ size is accompanied by the increased number of galanin-immunoreactive neurons and increased galanin content in parts of the colon located close to the tumour. Galanin, a neuroprotective peptide, may inhibit the extrinsic pathway of apoptosis and in this way promote cancer cell survival. The possible role of acetylcholine and some ENS neuropeptides was also discussed. Invasion of cancer cells spreads along nerve fibres with the involvement of locally-released neutrophins which promote, via their specific receptors, cancer cell proliferation and pro-survival signalling pathways. Thus, during CRC development cancer cells and neurons of the ENS release many neurotransmitters/neuropeptides which affect key cellular signalling pathways promoting cancer cell proliferation and pro-survival phenotype. The multiple interactions between ENS neurons, cancer cells and other cell types present in the colon wall increase cancer cell invasiveness and have a negative impact on the course of CRC.

scholarly journals Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiantian Tang ◽  
Guiying Wang ◽  
Sihua Liu ◽  
Zhaoxue Zhang ◽  
Chen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

scholarly journals The potential oncogenic and MLN4924-resistant effects of CSN5 on cervical cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract Background CSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet. Methods Data from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 and clinical relevance in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR–CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. The biological behaviors were analyzed by CCK8, clone formation assay, 3-D spheroid generation assay and cell cycle assay. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. MLN4924 was given in Siha and Hela with CSN5 overexpression. Results We found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells. Conclusions Our findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

scholarly journals Characterising the Response of Human Breast Cancer Cells to Polyamine Modulation

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 743
Author(s):  
Oluwaseun Akinyele ◽  
Heather M. Wallace
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Growth Responses ◽  
Cancer Management ◽  
Mcf 7

Breast cancer is a complex heterogeneous disease with multiple underlying causes. The polyamines putrescine, spermidine, and spermine are polycationic molecules essential for cell proliferation. Their biosynthesis is upregulated in breast cancer and they contribute to disease progression. While elevated polyamines are linked to breast cancer cell proliferation, there is little evidence to suggest breast cancer cells of different hormone receptor status are equally dependent on polyamines. In this study, we characterized the responses of two breast cancer cells, ER+ (oestrogen receptor positive) MCF-7 and ER- MDA-MB-231 cell lines, to polyamine modulation and determined the requirement of each polyamine for cancer cell growth. The cells were exposed to DFMO (a polyamine pathway inhibitor) at various concentrations under different conditions, after which several growth parameters were determined. Exposure of both cell lines to DFMO induced differential growth responses, MCF-7 cells showed greater sensitivity to polyamine pathway inhibition at various DFMO concentrations than the MDA-MB-231 cells. Analysis of intracellular DFMO after withdrawal from growth medium showed residual DFMO in the cells with concomitant decreases in polyamine content, ODC protein level, and cell growth. Addition of exogenous polyamines reversed the cell growth inhibition, and this growth recovery appears to be partly dependent on the spermidine content of the cell. Similarly, DFMO exposure inhibits the global translation state of the cells, with spermidine addition reversing the inhibition of translation in the breast cancer cells. Taken together, these data suggest that breast cancer cells are differentially sensitive to the antitumour effects of polyamine depletion, thus, targeting polyamine metabolism might be therapeutically beneficial in breast cancer management based on their subtype.

The Potential Oncogenic and MLN4924-Resistant Effects of CSN5 on Cervical Cancer Cells

2021 ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract BackgroundsCSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.MethodsData from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR-CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. CCK8, clone formation assay and cell cycle assay were also employed. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. Moreover, MLN4924 was applied in Siha and Hela with CSN5 overexpression.ResultsWe found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.ConclusionsOur findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

scholarly journals How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation?

2011 ◽  
Vol 108 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Mu Yao ◽  
Chanlu Xie ◽  
Maryrose Constantine ◽  
Sheng Hua ◽  
Brett D. Hambly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
East Asia ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Prostate Cancer Cells ◽  
The Mediterranean

We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2′-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.

scholarly journals Blocking IL-6/GP130 Signaling Inhibits Cell Viability/Proliferation, Glycolysis, and Colony Forming Activity in Human Pancreatic Cancer Cells

2019 ◽  
Vol 19 (5) ◽  
pp. 417-427 ◽  
Author(s):  
Xiang Chen ◽  
Jilai Tian ◽  
Gloria H. Su ◽  
Jiayuh Lin
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Human Pancreatic Cancer ◽  
Multiple Cancer ◽  
Pancreatic Cancer Cells ◽  
Stat3 Phosphorylation

Background:Elevated production of the pro-inflammatory cytokine interleukin-6 (IL-6) and dysfunction of IL-6 signaling promotes tumorigenesis and are associated with poor survival outcomes in multiple cancer types. Recent studies showed that the IL-6/GP130/STAT3 signaling pathway plays a pivotal role in pancreatic cancer development and maintenance.Objective:We aim to develop effective treatments through inhibition of IL-6/GP130 signaling in pancreatic cancer.Methods:The effects on cell viability and cell proliferation were measured by MTT and BrdU assays, respectively. The effects on glycolysis was determined by cell-based assays to measure lactate levels. Protein expression changes were evaluated by western blotting and immunoprecipitation. siRNA transfection was used to knock down estrogen receptor α gene expression. Colony forming ability was determined by colony forming cell assay.Results:We demonstrated that IL-6 can induce pancreatic cancer cell viability/proliferation and glycolysis. We also showed that a repurposing FDA-approved drug bazedoxifene could inhibit the IL-6/IL-6R/GP130 complexes. Bazedoxifene also inhibited JAK1 binding to IL-6/IL-6R/GP130 complexes and STAT3 phosphorylation. In addition, bazedoxifene impeded IL-6 mediated cell viability/ proliferation and glycolysis in pancreatic cancer cells. Consistently, other IL-6/GP130 inhibitors SC144 and evista showed similar inhibition of IL-6 stimulated cell viability, cell proliferation and glycolysis. Furthermore, all three IL-6/GP130 inhibitors reduced the colony forming ability in pancreatic cancer cells.Conclusion:Our findings demonstrated that IL-6 stimulates pancreatic cancer cell proliferation, survival and glycolysis, and supported persistent IL-6 signaling is a viable therapeutic target for pancreatic cancer using IL-6/GP130 inhibitors.

Genome-Wide Methylation Analysis Identifies NOX4 and KDM5A as Key Regulators in Inhibiting Breast Cancer Cell Proliferation by Ginsenoside Rg3

2018 ◽  
Vol 46 (06) ◽  
pp. 1333-1355 ◽  
Author(s):  
Juyeon Ham ◽  
Seungyeon Lee ◽  
Hyunkyung Lee ◽  
Dawoon Jeong ◽  
Sungbin Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Growth Effect ◽  
Breast Cancer Patients ◽  
Ginsenoside Rg3 ◽  
Methylation Analysis ◽  
Genome Wide

Ginsenoside Rg3 is a key metabolite of ginseng and is known to inhibit cancer cell growth. However, the epigenetics of CpG methylation and its regulatory mechanism have yet to be determined. Genome-wide methylation analysis of MCF-7 breast cancer cells treated with Rg3 was performed to identify epigenetically regulated genes and pathways. The effect of Rg3 on apoptosis and cell proliferation was examined by a colony formation assay and a dye-based cell proliferation assay. The association between methylation and gene expression was monitored by RT-PCR and Western blot analysis. Genome-wide methylation analysis identified the “cell morphology”-related pathway as the top network. Rg3 induced late stage apoptosis but inhibited cell proliferation up to 60%. Hypermethylated TRMT1L, PSMC6 and NOX4 were downregulated by Rg3, while hypomethylated ST3GAL4, RNLS and KDM5A were upregulated. In accordance, downregulation of NOX4 by siRNA abrogated the cell growth effect of Rg3, while the effect was opposite for KDM5A. Notably, breast cancer patients with a higher expression of NOX4 and KDM5A showed poor and good prognosis of survival, respectively. In conclusion, Rg3 deregulated tumor-related genes through alteration of the epigenetic methylation level leading to growth inhibition of cancer cells.

scholarly journals Gestational Tissue-Derived Human Mesenchymal Stem Cells Use Distinct Combinations of Bioactive Molecules to Suppress the Proliferation of Human Hepatoblastoma and Colorectal Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Nitchapon Paiboon ◽  
Witchayaporn Kamprom ◽  
Sirikul Manochantr ◽  
Chairat Tantrawatpan ◽  
Duangrat Tantikanlayaporn ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Mesenchymal Stem Cells ◽  
Bioactive Molecules ◽  
Mass Spectrometry Analysis ◽  
Cancer Cell Proliferation ◽  
Protein Fractionation ◽  
Spectrometry Analysis ◽  
Colorectal Cancer Cells

Background. Cancer has been considered a serious global health problem and a leading cause of morbidity and mortality worldwide. Despite recent advances in cancer therapy, treatments of advance stage cancers are mostly ineffective resulting in poor survival of patients. Recent evidences suggest that multipotent human mesenchymal stem cells (hMSCs) play important roles in growth and metastasis of several cancers by enhancing their engraftment and inducing tumor neovascularization. However, the effect of hMSCs on cancer cells is still controversial because there are also evidences demonstrating that hMSCs inhibited growth and metastasis of some cancers. Methods. In this study, we investigated the effects of bioactive molecules released from bone marrow and gestational tissue-derived hMSCs on the proliferation of various human cancer cells, including C3A, HT29, A549, Saos-2, and U251. We also characterized the hMSC-derived factors that inhibit cancer cell proliferation by protein fractionation and mass spectrometry analysis. Results. We herein make a direct comparison and show that the effects of hMSCs on cancer cell proliferation and migration depend on both hMSC sources and cancer cell types and cancer-derived bioactive molecules did not affect the cancer suppressive capacity of hMSCs. Moreover, hMSCs use distinct combination of bioactive molecules to suppress the proliferation of human hepatoblastoma and colorectal cancer cells. Using protein fractionation and mass spectrometry analysis, we have identified several novel hMSC-derived factors that might be able to suppress cancer cell proliferation. Conclusion. We believe that the procedure developed in this study could be used to discover other therapeutically useful molecules released by various hMSC sources for a future in vivo study.

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