scholarly journals Lysophosphatidic Acid: Promoter of Cancer Progression and of Tumor Microenvironment Development. A Promising Target for Anticancer Therapies?

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1390
Author(s):  
Sistiana Aiello ◽  
Federica Casiraghi
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Cancer Progression ◽  
Lysophosphatidic Acid ◽  
Immune Surveillance ◽  
Primary Tumors ◽  
Invasion And Migration ◽  
Cell Functions ◽  
Promising Target ◽  
And Migration

Increased expression of the enzyme autotaxin (ATX) and the consequently increased levels of its product, lysophosphatidic acid (LPA), have been reported in several primary tumors. The role of LPA as a direct modulator of tumor cell functions—motility, invasion and migration capabilities as well as resistance to apoptotic death—has been recognized by numerous studies over the last two decades. Notably, evidence has recently been accumulating that shows that LPA also contributes to the development of the tumor microenvironment (TME). Indeed, LPA plays a crucial role in inducing angiogenesis and lymphangiogenesis, triggering cellular glycolytic shift and stimulating intratumoral fibrosis. In addition, LPA helps tumoral cells to escape immune surveillance. Treatments that counter the TME components, in order to deprive cancer cells of their crucial support, have been emerging among the promising new anticancer therapies. This review aims to summarize the latest knowledge on how LPA influences both tumor cell functions and the TME by regulating the activity of its different elements, highlighting why and how LPA is worth considering as a molecular target for new anticancer therapies.

scholarly journals Nature vs. Nurture: The Two Opposing Behaviors of Cytotoxic T Lymphocytes in the Tumor Microenvironment

2021 ◽  
Vol 22 (20) ◽  
pp. 11221
Author(s):  
Nagaja Capitani ◽  
Laura Patrussi ◽  
Cosima T. Baldari
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cytotoxic T Cells ◽  
Dual Nature ◽  
And Migration ◽  
Nature Vs Nurture

Similar to Janus, the two-faced god of Roman mythology, the tumor microenvironment operates two opposing and often conflicting activities, on the one hand fighting against tumor cells, while on the other hand, favoring their proliferation, survival and migration to other sites to establish metastases. In the tumor microenvironment, cytotoxic T cells—the specialized tumor-cell killers—also show this dual nature, operating their tumor-cell directed killing activities until they become exhausted and dysfunctional, a process promoted by cancer cells themselves. Here, we discuss the opposing activities of immune cells populating the tumor microenvironment in both cancer progression and anti-cancer responses, with a focus on cytotoxic T cells and on the molecular mechanisms responsible for the efficient suppression of their killing activities as a paradigm of the power of cancer cells to shape the microenvironment for their own survival and expansion.

scholarly journals Mast Cell-Derived SAMD14 is a Novel Regulator of the Human Prostate Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1237
Author(s):  
Linda K. H. Teng ◽  
Brooke A. Pereira ◽  
Shivakumar Keerthikumar ◽  
Cheng Huang ◽  
Birunthi Niranjan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Extracellular Matrix ◽  
Tumor Microenvironment ◽  
Suppressor Gene ◽  
Prostate Tumor ◽  
Human Prostate ◽  
Proteomic Profiling ◽  
Putative Tumor Suppressor Gene ◽  
Invasion And Migration ◽  
And Migration

Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs), which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remain poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed that overexpression of SAMD14 in HMC-1 altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data present the first profile of human MCs derived from prostate cancer patient specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.

scholarly journals YB-1 Is Altered in Pregnancy-Associated Disorders and Affects Trophoblast in Vitro Properties via Alternation of Multiple Molecular Traits

2021 ◽  
Vol 22 (13) ◽  
pp. 7226
Author(s):  
Violeta Stojanovska ◽  
Aneri Shah ◽  
Katja Woidacki ◽  
Florence Fischer ◽  
Mario Bauer ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Cell Function ◽  
Trophoblast Cell ◽  
Mrna Levels ◽  
Trophoblast Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Apoptosis And Inflammation

Cold shock Y-box binding protein-1 (YB-1) coordinates several molecular processes between the nucleus and the cytoplasm and plays a crucial role in cell function. Moreover, it is involved in cancer progression, invasion, and metastasis. As trophoblast cells share similar characteristics with cancer cells, we hypothesized that YB-1 might also be necessary for trophoblast functionality. In samples of patients with intrauterine growth restriction, YB-1 mRNA levels were decreased, while they were increased in preeclampsia and unchanged in spontaneous abortions when compared to normal pregnant controls. Studies with overexpression and downregulation of YB-1 were performed to assess the key trophoblast processes in two trophoblast cell lines HTR8/SVneo and JEG3. Overexpression of YB-1 or exposure of trophoblast cells to recombinant YB-1 caused enhanced proliferation, while knockdown of YB-1 lead to proliferative disadvantage in JEG3 or HTR8/SVneo cells. The invasion and migration properties were affected at different degrees among the trophoblast cell lines. Trophoblast expression of genes mediating migration, invasion, apoptosis, and inflammation was altered upon YB-1 downregulation. Moreover, IL-6 secretion was excessively increased in HTR8/SVneo. Ultimately, YB-1 directly binds to NF-κB enhancer mark in HTR8/SVneo cells. Our data show that YB-1 protein is important for trophoblast cell functioning and, when downregulated, leads to trophoblast disadvantage that at least in part is mediated by NF-κB.

scholarly journals MENA promotes esophageal squamous cell carcinoma cell invasion and migration via MMP-2, MMP-9 and AKT activation

2020 ◽  
Author(s):  
Yueheng Li ◽  
Na Gao ◽  
Jing Li ◽  
Zhengfan Gao ◽  
Zhenzhen Yang ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Invasion ◽  
Tumor Cell Invasion ◽  
Wound Healing Assay ◽  
Transwell Assay ◽  
Invasion And Migration ◽  
Akt Activation ◽  
Qrt Pcr ◽  
And Migration ◽  
Migration Capacity

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is a fatal disease with poor prognosis. The predominant reason for ESCC-related death is metastasis caused by tumor cell invasion. Human MENA protein is a member of Ena/Vasp family, which plays a critical role during tumor cell invasion. However, the biological effect of MENA in ESCC cell lines remains unclear Methods: In this study, fluorescent quantitative real-time PCR (qRT-PCR) were conducted to detect the mRNA expression of MENA in tumor and para-cancer tissue, CCK-8 assay and clone formation assay were conducted to evaluate cell proliferation activity, Transwell assay and wound-healing assay were conducted to detect the changes of cell invasion and migration capacity, siRNA and MENA expression vector were constructed to explore biological function of MENA in ESCC cell lines. Western blot analysis were conducted to detect the expressions of MENA , molecular markers of epithelial-mesenchymal transition (EMT), Akt, p-Akt, MMP-2 and MMP-9 respectively in ESCC cell line. Results: The qRT-PCR experiment results showed that MENA expression in ESCC tissue of 35 patients was relatively higher than that in tissue adjacent to cancer. CCK-8 assay suggested that tumor cell proliferation capacity was suppressed followed by the knockdown of MENA expression in Mena high ESCC cell TE13 and was potentiated by the overexpression of MENA in Mena low ESCC cell TE1. Transwell assay and wound healing assay demonstrated that interfering in MENA could inhibit TE13 cells invasion and migration capacity by affecting the expressions of Matrix metalloproteinase-2(MMP-2) and Matrix metalloproteinase-9 (MMP-9), in contrast, overexpression of MENA in Mena low ESCC cell TE1 could promote invasion and migration by up-regulated expression of MMP-2 and MMP-9. Western blot analysis indicated that interfering of MENA expression could affect EMT-related molecular markers (E-cadherin, N-cadherin, Snail, Slug), Akt and p-Akt Conclusions: Our study reveal that MENA could promote the ESCC cell invasion and migration by upregulate MMP-2, MMP-9 expression and Akt activation. Meanwhile, interfering of MENA expression could affect EMT in ESCC cells. This indicated that MENA may be a potential molecular therapeutic target for ESCC metastasis

scholarly journals Iron as a Central Player and Promising Target in Cancer Progression

2019 ◽  
Vol 20 (2) ◽  
pp. 273 ◽  
Author(s):  
Michaela Jung ◽  
Christina Mertens ◽  
Elisa Tomat ◽  
Bernhard Brüne
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Cancer Progression ◽  
Crucial Role ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Tumor Therapy ◽  
Essential Element ◽  
Major Function ◽  
Iron Pool

Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.

scholarly journals Influence of the microenvironment on cell fate determination and migration

2014 ◽  
Vol 46 (9) ◽  
pp. 309-314 ◽  
Author(s):  
Alexander B. Bloom ◽  
Muhammad H. Zaman
Keyword(s):  
Tumor Microenvironment ◽  
Cell Fate ◽  
Tumor Metastasis ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Cell Functions ◽  
Cellular Machinery ◽  
And Migration ◽  
Cellular Fate

Several critical cell functions are influenced not only by internal cellular machinery but also by external mechanical and biochemical cues from the surrounding microenvironment. Slight changes to the microenvironment can result in dramatic changes to the cell's phenotype; for example, a change in the nutrients or pH of a tumor microenvironment can result in increased tumor metastasis. While cellular fate and the regulators of cell fate have been studied in detail for several decades now, our understanding of the extracellular regulators remains qualitative and far from comprehensive. In this review, we discuss the microenvironment influence on cell fate in terms of adhesion, migration, and differentiation and focus on both developments in experimental and computation tools to analyze cellular fate.

scholarly journals MYC as a Multifaceted Regulator of Tumor Microenvironment Leading to Metastasis

2020 ◽  
Vol 21 (20) ◽  
pp. 7710
Author(s):  
Erna Marija Meškytė ◽  
Sabiha Keskas ◽  
Yari Ciribilli
Keyword(s):  
Tumor Microenvironment ◽  
Treatment Strategies ◽  
Invasion And Migration ◽  
Over Expression ◽  
Novel Studies ◽  
Expression Of Genes ◽  
Promote Tumor Growth ◽  
Infiltrating Cells ◽  
Metastasis Development ◽  
And Migration

The Myc family of oncogenes is deregulated in many types of cancer, and their over-expression is often correlated with poor prognosis. The Myc family members are transcription factors that can coordinate the expression of thousands of genes. Among them, c-Myc (MYC) is the gene most strongly associated with cancer, and it is the focus of this review. It regulates the expression of genes involved in cell proliferation, growth, differentiation, self-renewal, survival, metabolism, protein synthesis, and apoptosis. More recently, novel studies have shown that MYC plays a role not only in tumor initiation and growth but also has a broader spectrum of functions in tumor progression. MYC contributes to angiogenesis, immune evasion, invasion, and migration, which all lead to distant metastasis. Moreover, MYC is able to promote tumor growth and aggressiveness by recruiting stromal and tumor-infiltrating cells. In this review, we will dissect all of these novel functions and their involvement in the crosstalk between tumor and host, which have demonstrated that MYC is undoubtedly the master regulator of the tumor microenvironment. In sum, a better understanding of MYC’s role in the tumor microenvironment and metastasis development is crucial in proposing novel and effective cancer treatment strategies.

scholarly journals Corilagin Represses Epithelial to Mesenchymal Transition Process Through Modulating Wnt/β-Catenin Signaling Cascade

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1406 ◽  
Author(s):  
Sun Tae Hwang ◽  
Min Hee Yang ◽  
Alan Prem Kumar ◽  
Gautam Sethi ◽  
Kwang Seok Ahn
Keyword(s):  
Tumor Cells ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Transition Process ◽  
Carcinoma Cells ◽  
Signaling Cascade ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Anti Cancer ◽  
And Migration

Corilagin (CLG), a major component of several medicinal plants, can exhibit diverse pharmacological properties including those of anti-cancer, anti-inflammatory, and hepatoprotective qualities. However, there are no prior studies on its potential impact on the epithelial-to-mesenchymal transition (EMT) process. EMT can lead to dissemination of tumor cells into other organs and promote cancer progression. Hence, we aimed to investigate the effect of CLG on EMT and its mechanism(s) of action in tumor cells. We noted that CLG reduced the expression of various epithelial markers and up-regulated the expression of Occludin and E-cadherin in both basal and TGFβ-stimulated tumor cells. CLG treatment also abrogated cellular invasion and migration in colon and prostate carcinoma cells. In addition, CLG effectively attenuated the Wnt/β-catenin signaling cascade in TGFβ-stimulated cells. Overall, our study suggests that CLG may function as and effective modulator of EMT and metastasis in neoplastic cells.

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