Role of angiogenesis factors in formation of metastatic niches.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15534-e15534
Author(s):  
Elena M. Frantsiyants ◽  
Oleg I. Kit ◽  
Irina V. Kaplieva ◽  
Yuriy A. Gevorkyan ◽  
Natalya V. Soldatkina ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factors ◽  
Tumor Cells ◽  
Comparison Group ◽  
Metastatic Tumor ◽  
Specific Cell ◽  
Cell Type ◽  
Metastatic Niche ◽  
Mesenchymal Transition

e15534 Background: A metastatic niche indicates a particular location with a specific cell type, epidermal-mesenchymal transition proteins and diffuse signals that are necessary for the growth of metastases. The purpose of the study was to determine levels of VEGFs, their receptors and TGFβ1 in tissues of gastric cancer (GC) and its metastatic niches: the peritoneum and omentum. Methods: The main group included 21 patients with metastatic GC T3-4аN0-3M1; comparison group – 17 non-cancer patients. Levels of VEGFA, VEGFC, sVEGFR1, sVEGFR3 and TGFβ1 in tissues were determined by standard ELISA methods. Results: Levels of growth factors in GC tissues were higher than in controls: VEGFA in T3-4аN0-3M1 – by 2.7 times, in T3-4аN0-3M0 – by 2.5 times; TGFβ1 in T3-4аN0-3M1 – by 5.6 times, in T3-4аN0-3M0 – by 3.5 times. VEGFA levels in primary gastric tumors were similar in all patients, while TGFβ1 in T3-4аN0-3M1 was 1.6 times (p < 0.05) higher than in T3-4аN0-3M0. VEGFA levels in T3-4аN0-3M1 exceeded control values: in the omentum – by 2.8, in the peritoneum – by 4.2 times. TGFβ1 in the omentum and peritoneum in T3-4аN0-3M1 was increased by 2.5 and 3.1 times respectively, compared to controls. Statistically significant differences in VEGFA and TGFβ1 levels in the omentum and peritoneum in T3-4аN0-3M0 were not found. Conclusions: GC is characterized by equally elevated levels of VEGFA, regardless of the presence or absence of metastases. In the omentum and peritoneum with metastases, high VEGF levels can be considered as one of the primary factors for the formation of signaling pathways between metastatic tumor cells and local non-tumor cells in premetastatic niches. Levels of TGFβ1 in the omentum and peritoneum increase only in patients with metastases, and in GC tissue they are increased to a greater extent than in patients without metastases. Probably, in case of T3-4aN0-3M0, the factor produced by the primary tumor was insufficient for its paracrine induction in the metastatic niche, and scattered cells could not transit from “sleeping” to the active state.

Markers of a metastatic niche in the omentum in ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18081-e18081
Author(s):  
Tatiana I. Moiseenko ◽  
Elena M. Frantsiyants ◽  
Irina V. Kaplieva ◽  
Valeria A. Bandovkina ◽  
Natalia D. Cheryarina ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Growth Factors ◽  
Tumor Cells ◽  
Comparison Group ◽  
Metastatic Tumor ◽  
Main Group ◽  
Control Group ◽  
Metastatic Niche ◽  
Primary Tumors ◽  
Igf I

e18081 Background: Ovarian cancer spreads intraperitoneally due to the interaction of tumor cells and the omental mesothelium, creating a metastatic niche and supporting elements of cancer cell expansion such as adhesion, proliferation, migration, and neoangiogenesis. The purpose of the study was to analyze levels of VEGFA, IGF-I, IGF-II and TGFβ1 in omental tissues in ovarian cancer (OC). Methods: The main group included 23 patients with metastatic OC T3-4аN0-3M1; the comparison group – 21 patients with non-metastatic OC T3-4аN0-3M0; the control group – 19 non-cancer patients. Levels of VEGFA, IGF-I, IGF-II and TGFβ1 were measured by standard ELISA methods in tissues of primary tumors and the omentum. Results: Levels of growth factors in the comparison group were not elevated compared to control values. Growth factors in omental tissues in the main group were increased compared to control values: VEGFA – by 2.5 times, IGF-I – by 3.4 times, IGF-II – by 2.5 times, TGFβ1 - by 3.1 times. In the comparison group, the levels in omental tissues were lower than in the main group: VEGFA – by 1.7 times (p < 0.05), IGF-I – by 2.1 times, IGF-II – by 1.6 times (p < 0.05); TGFβ1 did not differ from the levels in the main group. Conclusions: Higher expression of VEGFА in the omentum with metastases can be considered a significant factor in the formation of signaling pathways between metastatic tumor cells and local non-cancer cells. IGF-I and IGF-II trigger the endothelial growth factor. The TGFβ1 activation in the omentum in metastatic ovarian cancer is necessary for the paracrine induction and transition of disseminated tumor and/or stem cells from the "sleeping" to the active state.

scholarly journals The dynamic behavior of lipid droplets in the pre-metastatic niche

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Metastatic Tumor ◽  
Current Evidence ◽  
Biological Functions ◽  
Metastatic Niche ◽  
Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

Current Study of RhoA and Associated Signaling Pathways in Gastric Cancer

2020 ◽  
Vol 15 (7) ◽  
pp. 607-613 ◽  
Author(s):  
Haiping Liu ◽  
Yiqian Liu ◽  
Xiaochuan Zhang ◽  
Xiaodong Wang
Keyword(s):  
Gastric Cancer ◽  
Survival Rate ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Actin Polymerization ◽  
Cell Transformation ◽  
Cell Movement ◽  
Invasion And Metastasis ◽  
Common Cancer

Gastric cancer (GC) is the fourth-most common cancer in the world, with an estimated 1.034 million new cases in 2015, and the third-highest cause of cancer deaths, estimated at 785,558, in 2014. Early diagnosis and treatment greatly affect the survival rate in patients with GC: the 5‐year survival rate of early GC reaches 90%‐95%, while the mortality rate significantly increases if GC develops to the late stage. Recently, studies for the role of RhoA in the diseases have become a hot topic, especially in the development of tumors. A study found that RhoA can regulate actin polymerization, cell adhesion, motor-myosin, cell transformation, and the ability to participate in the activities of cell movement, proliferation, migration, which are closely related to the invasion and metastasis of tumor cells. However, the specific role of RhoA in tumor cells remains to be studied. Therefore, our current study aimed to briefly review the role of RhoA in GC, especially for its associated signaling pathways involved in the GC progression.

scholarly journals Cell Plasticity and Prostate Cancer: The Role of Epithelial–Mesenchymal Transition in Tumor Progression, Invasion, Metastasis and Cancer Therapy Resistance

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2795
Author(s):  
Sofia Papanikolaou ◽  
Aikaterini Vourda ◽  
Spyros Syggelos ◽  
Kostis Gyftopoulos
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Tumor Progression ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Tumor ◽  
Therapy Resistance ◽  
Cellular Process ◽  
Cell Plasticity ◽  
Mesenchymal Transition

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

scholarly journals Expression of Villin associated with Epithelial to Mesenchymal Transition in patients with gastric cancer relating to their clinical and morphological specifications

2020 ◽  
Vol 5 (1) ◽  
pp. 11-14
Author(s):  
Seyed Mohammad Azizi ◽  
Mehrdad Hashemi ◽  
Sarvenaz Falsafi ◽  
Seyedeh Mina Azizi ◽  
Reza Shirkoohi
Keyword(s):  
Gastric Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Tissue ◽  
Tissue Type ◽  
Actin Binding ◽  
Specific Cell ◽  
Cross Sectional ◽  
Mesenchymal Transition ◽  
Biological Phenomena ◽  
Two Samples

Aim and Background: Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related deaths. The metastatic invasive cells of tumor tissue are the main cause of mortality. Numerous biological phenomena are involved in organizing the metastatic process. The Epithelial to Mesenchymal Transition is one of the major mechanisms modulating malignant phenotypes by gastric epithelial cells. Specific cell signals are responsible for epithelial or mesenchymal maintenance of the cells in the tissue. These signals are evaluated by measuring the expression of epithelial and mesenchymal biomarkers in that tissue. Villin is an actin-binding protein mainly expressed in the brush border of epithelium which preserves the shape of the cell and its adhesion to the tissue. The aim of the present research is to study the expression of Villin in the cells as a feasible epithelial biomarker in order to evaluate the cross-sectional situation of the cells. Materials and Methods: 38 patients with gastric cancer that were admitted to the Cancer Institute of Imam Khomeini in a period of 6 months were chosen randomly. two samples were collected from each individual; one from the tumoral tissue and one from normal margin of the tumorous tissue. These samples were evaluated after obtaining informed consent from the patients. RNA was extracted from the samples and used as template for cDNA synthesis. The Villin expression was then measured through Real-Time PCR and statistical data according to tissue type and different grades were collected. Results: The expression of Villin in tumor tissue of the patients with gastric cancer was significantly lower than the normal tissue. Conclusion: As it appears decreased expression of Villin can act as an effective factor toward loss of epithelial nature of the cell and occurring Epithelial to Mesenchymal Transition followed by metastasis.

scholarly journals Hepatocyte-tumor cell interaction in vitro. I. Conditions for rosette formation and inhibition by anti-H-2 antibody.

1980 ◽  
Vol 151 (4) ◽  
pp. 984-989 ◽  
Author(s):  
V Schirrmacher ◽  
R Cheingsong-Popov ◽  
H Arnheiter
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Metastatic Tumor ◽  
Cell Interaction ◽  
Rosette Formation ◽  
Normal Cells ◽  
Neuraminidase Treatment

Murine hepatocytes, isolated by an in situ collagenase-perfusion technique and cultured in Petri dishes, were shown to form rosettes with liver-metastasizing syngeneic tumor cells. Pretreatment of the tumor cells with neuraminidase generally increased the binding, whereas pretreatment of the liver cells with neuraminidase abolished the binding completely. The tumor-cell binding may be mediated by the previously described lectin-like receptor of hepatocytes that also was sensitive to neuraminidase treatment and that bound desialylated cells better than normal cells. Anti-H-2 sera could efficiently inhibit the rosette formation of metastatic tumor cells with the hepatocytes, which points to a possible role of H-2 molecules in this interaction of neoplastic and normal cells.

scholarly journals Mos in the Oocyte: How to Use MAPK Independently of Growth Factors and Transcription to Control Meiotic Divisions

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Aude Dupré ◽  
Olivier Haccard ◽  
Catherine Jessus
Keyword(s):  
Growth Factors ◽  
Transcriptional Activation ◽  
Biological Activities ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Mitogen Activated Protein Kinase ◽  
Specific Cell ◽  
Cell Type ◽  
Specific Cell Type ◽  
Mitogen Activated Protein

In many cell types, the mitogen-activated protein kinase (MAPK) also named extracellular signal-regulated kinase (ERK) is activated in response to a variety of extracellular growth factor-receptor interactions and leads to the transcriptional activation of immediate early genes, hereby influencing a number of tissue-specific biological activities, as cell proliferation, survival and differentiation. In one specific cell type however, the female germ cell, MAPK does not follow this canonical scheme. In oocytes, MAPK is activated independently of growth factors and tyrosine kinase receptors, acts independently of transcriptional regulation, plays a crucial role in controlling meiotic divisions, and is under the control of a peculiar upstream regulator, the kinase Mos. Mos was originally identified as the transforming gene of Moloney murine sarcoma virus and its cellular homologue was the first proto-oncogene to be molecularly cloned. What could be the specific roles of Mos that render it necessary for meiosis? Which unique functions could explain the evolutionary cost to have selected one gene to only serve for few hours in one very specific cell type? This review discusses the original features of MAPK activation by Mos and the roles of this module in oocytes.

scholarly journals When the endothelium scores an own goal: endothelial cells actively augment metastatic extravasation through endothelial-mesenchymal transition

2016 ◽  
Vol 310 (9) ◽  
pp. H1055-H1063 ◽  
Author(s):  
Ákos Gasparics ◽  
László Rosivall ◽  
István A. Krizbai ◽  
Attila Sebe
Keyword(s):  
Endothelial Cells ◽  
Tumor Cells ◽  
Metastatic Tumor ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
New Therapeutic Approaches ◽  
Pathological Conditions ◽  
Junctional Protein ◽  
Endothelial Mesenchymal Transition ◽  
Organ Fibrosis

Endothelial-mesenchymal transition (EndMT) is an important mechanism during organ development and in certain pathological conditions. For example, EndMT contributes to myofibroblast formation during organ fibrosis, and it has been identified as an important source of cancer-associated fibroblasts, facilitating tumor progression. Recently, EndMT was proposed to modulate endothelial function during intravasation and extravasation of metastatic tumor cells. Evidence suggests that endothelial cells are not passive actors during transendothelial migration (TEM) of cancer cells, as there are profound changes in endothelial junctional protein expression, signaling, permeability, and contractility. This review describes these alterations in endothelial characteristics during TEM of metastatic tumor cells and discusses them in the context of EndMT. EndMT could play an important role during metastatic intravasation and extravasation, a novel hypothesis that may lead to new therapeutic approaches to tackle metastatic disease.

Sign in / Sign up

Export Citation Format

Share Document