Cancer-Associated Fibroblasts Differentiated by Exosomes Isolated from Cancer Cells Promote Cancer Cell Invasion

Cancer-associated fibroblasts (CAFs) in the cancer microenvironment play an essential role in metastasis. Differentiation of endothelial cells into CAFs is induced by cancer cell-derived exosomes secreted from cancer cells that transfer molecular signals to surrounding cells. Differentiated CAFs facilitate migration of cancer cells to different regions through promoting extracellular matrix (ECM) modifications. However, in vitro models in which endothelial cells exposed to cancer cell-derived exosomes secreted from various cancer cell types differentiate into CAFs or a microenvironmentally controlled model for investigating cancer cell invasion by CAFs have not yet been studied. In this study, we propose a three-dimensional in vitro cancer cell invasion model for real-time monitoring of the process of forming a cancer invasion site through CAFs induced by exosomes isolated from three types of cancer cell lines. The invasiveness of cancer cells with CAFs induced by cancer cell-derived exosomes (eCAFs) was significantly higher than that of CAFs induced by cancer cells (cCAFs) through physiological and genetic manner. In addition, different genetic tendencies of the invasion process were observed in the process of invading cancer cells according to CAFs. Our 3D microfluidic platform helps to identify specific interactions among multiple factors within the cancer microenvironment and provides a model for cancer drug development.

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Tumoral Neuroligin 1 Promotes Cancer–Nerve Interactions and Synergizes with the Glial Cell Line-Derived Neurotrophic Factor

Cells ◽

10.3390/cells11020280 ◽

2022 ◽

Vol 11 (2) ◽

pp. 280

Author(s):

Laura Bizzozero ◽

Margherita Pergolizzi ◽

Davide Pascal ◽

Elena Maldi ◽

Giulia Villari ◽

...

Keyword(s):

Cancer Cells ◽

Cell Line ◽

Glial Cell ◽

Cancer Cell ◽

Cell Invasion ◽

Neurotrophic Factor ◽

Regulatory Protein ◽

Cancer Cell Invasion

Many nervous proteins are expressed in cancer cells. In this report, we asked whether the synaptic protein neuroligin 1 (NLGN1) was expressed by prostatic and pancreatic carcinomas; in addition, given the tendency of these tumors to interact with nerves, we asked whether NLGN1 played a role in this process. Through immunohistochemistry on human tissue microarrays, we showed that NLGN1 is expressed by prostatic and pancreatic cancer tissues in discrete stages and tumor districts. Next, we performed in vitro and in vivo assays, demonstrating that NLGN1 promotes cancer cell invasion and migration along nerves. Because of the established role of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) in tumor–nerve interactions, we assessed a potential NLGN1–GDNF cooperation. We found that blocking GDNF activity with a specific antibody completely inhibited NLGN1-induced in vitro cancer cell invasion of nerves. Finally, we demonstrated that, in the presence of NLGN1, GDNF markedly activates cofilin, a cytoskeletal regulatory protein, altering filopodia dynamics. In conclusion, our data further prove the existence of a molecular and functional cross-talk between the nervous system and cancer cells. NLGN1 was shown here to function along one of the most represented neurotrophic factors in the nerve microenvironment, possibly opening new therapeutic avenues.

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The antihyperlipidemic drug Potassium Piperate impairs migration and tumorgenesis of breast cancer cells via upregulation of miR-31

10.21203/rs.3.rs-290044/v1 ◽

2021 ◽

Author(s):

Junping Lu ◽

Xiaoxia Tian ◽

Mailisu Mailisu ◽

Morigen Morigen ◽

Lifei Fan

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Invasion ◽

Combination Treatment ◽

Breast Cancer Cells ◽

Target Genes ◽

Cancer Cell Invasion

Abstract Background Breast cancer is a leading malignant tumor which causes deaths among women, and metastasis is the primary cause for mortality in breast cancer. Due to the involvement of many regulatory molecules and signaling pathways, the occurrence and development process of metastasis needs to be further studied. MicroRNAs (miRNAs) are ubiquitously expressed small non-coding RNAs that have been shown to play an important role in the diagnosis and treatment of many diseases, as well as constituting an attractive candidate to control metastasis. In this study, we tried to uncover the mechanism of GBK in impairing breast cancer cell invasion and metastasis.Methods We treated cancer cells with GBK or not, found its target miRNA by analyzed miRNA transcriptional changes and the miRNA target genes by performed with the QT-PCR and Western Blot. The proliferation of breast cancer cells in vitro and in vivo under combination treatment with GBK and DDP was measured by CCK-8 kit and the nude mice tumor formation experiment.Results We found tumor suppressor miR-31 was a main target of GBK. GBK treatment affected the epigenetic modification at CpG sites by downregulating DNA methyltransferases, thus the methylation levels at CpG of lncRNA LOC554202 decreased significantly, and in turn upregulating of both miR-31 and its host gene LOC554202 in breast cancer cells. We also observed significant inhibition of miR-31 target genes under GBK stimulation, including RhoA, WAVE3 and SATB2, which all closely related to cancer cell invasion, migration and proliferation. Furthermore, we revealed that combination treatment with GBK and DDP had synergistic and dose reduction potential in inhibiting the proliferation of breast cancer cells in vitro and in vivo, especially in TNBC.Conclusion This study further analyzes the target and underlying mechanism of GBK in inhibiting breast cancer migration and invasion, and provides theoretical support for the development of GBK as an auxiliary drug for clinical treatment.

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CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion

Cancers ◽

10.3390/cancers13112745 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2745

Author(s):

Miran Jeong ◽

Yi-Yue Wang ◽

Ju-Yeon Choi ◽

Myong-Cheol Lim ◽

Jung-Hye Choi

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Invasion ◽

Ovarian Cancer Cell ◽

Ovarian Cancer Cells ◽

Human Ovarian Cancer ◽

Cancer Cell Invasion ◽

Cc Chemokine ◽

Chemokine Ligand

In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis.

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MATHEMATICAL MODELLING OF CANCER CELL INVASION OF TISSUE: THE ROLE OF THE UROKINASE PLASMINOGEN ACTIVATION SYSTEM

Mathematical Models and Methods in Applied Sciences ◽

10.1142/s0218202505000947 ◽

2005 ◽

Vol 15 (11) ◽

pp. 1685-1734 ◽

Cited By ~ 169

Author(s):

M. A. J. CHAPLAIN ◽

G. LOLAS

Keyword(s):

Cancer Cells ◽

Cancer Cell ◽

Cell Invasion ◽

The Body ◽

Plasminogen Activation ◽

Cancer Cell Invasion ◽

Plasminogen Activation System ◽

Activation System ◽

Spatio Temporal

The growth of solid tumours proceeds through two distinct phases: the avascular and the vascular phase. It is during the latter stage that the insidious process of cancer invasion of peritumoral tissue can and does take place. Vascular tumours grow rapidly allowing the cancer cells to establish a new colony in distant organs, a process that is known as metastasis. The progression from a single, primary tumour to multiple tumours in distant sites throughout the body is known as the metastatic cascade. This is a multistep process that first involves the over-expression by the cancer cells of proteolytic enzyme activity, such as the urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs). uPA itself initiates the activation of an enzymatic cascade that primarily involves the activation of plasminogen and subsequently its matrix degrading protein plasmin. Degradation of the matrix then enables the cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body. In this paper we consider a mathematical model of cancer cell invasion of tissue (extracellular matrix) which focuses on the role of the plasminogen activation system. The model consists of a system of reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, urokinase plasminogen activator (uPA), uPA inhibitors, plasmin and the host tissue. The focus of the modelling is on the spatio-temporal dynamics of the uPA system and how this influences the migratory properties of the cancer cells through random motility, chemotaxis and haptotaxis. The results obtained from numerical computations carried out on the model equations produce rich, dynamic heterogeneous spatio-temporal solutions and demonstrate the ability of rather simple models to produce complicated dynamics, all of which are associated with tumour heterogeneity and cancer cell progression and invasion.

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Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion

Cancer Letters ◽

10.1016/j.canlet.2009.04.013 ◽

2009 ◽

Vol 284 (1) ◽

pp. 80-85 ◽

Cited By ~ 95

Author(s):

Severin Pinilla ◽

Eckhard Alt ◽

F.J. Abdul Khalek ◽

Constantin Jotzu ◽

Fabian Muehlberg ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Cells ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cell Invasion ◽

Cancer Cell Invasion ◽

Breast Cancer Cell Invasion ◽

Resident Stem Cells ◽

Promote Breast Cancer

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α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3

The Journal of Cell Biology ◽

10.1083/jcb.201502040 ◽

2015 ◽

Vol 210 (6) ◽

pp. 1013-1031 ◽

Cited By ~ 72

Author(s):

Nikki R. Paul ◽

Jennifer L. Allen ◽

Anna Chapman ◽

Maria Morlan-Mairal ◽

Egor Zindy ◽

...

Keyword(s):

Cancer Cells ◽

Cell Invasion ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Cancer Cell Invasion ◽

Coupling Protein ◽

Α5β1 Integrin ◽

In Cells

Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo.

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