scholarly journals Induction of Proteases in Peritoneal Carcinomatosis, the Role of ICAM-1/CD43 Interaction

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Nawar A. Alkhamesi ◽  
Gretta Roberts ◽  
Paul Ziprin ◽  
David H. Peck ◽  
Ara W. Darzi
Keyword(s):  
Tumor Cells ◽  
Tumor Invasion ◽  
Direct Contact ◽  
Therapeutic Option ◽  
Gelatin Zymography ◽  
Cell Types ◽  
Vital Role ◽  
Indirect Contact ◽  
Clinical Issue

Introduction The development of peritoneal metastases is a significant clinical issue in the treatment of abdominal cancers and is associated with poor prognosis. We have previously shown that ICAM-1-CD43 interaction plays a significant role in tumor adhesion. However, an invasive phenotype is critical to establish tumor progression via cell associated and secreted proteases including matrix metalloproteinases. High metalloproteinases level significantly enhanced metastasis phenotype on tumors, a detrimental effect on surgical outcome. We investigated the role of direct and indirect signaling between the mesothelium and the tumor cells in enhancing tumor invasion and possible therapeutic intervention. Methods Mesothelial cells were enzymatically derived from human omental tissue and implanted in 24 wells plates. Colorectal cancer cells were then introduced and allowed a direct and an indirect contact with the mesothelial layer. Anti-ICAM antibodies, anti-CD43 antibodies, and heparin were used to block MMP production. Gelatin zymography was performed on the supernatant to detect MMPs activity. Results MMP production was observed in mesothelial and tumor cells. Direct contact between cell types enhanced MMP9 and 2 (p < 0.05). Indirect contact also stimulate MMPs but at a lower degree. ICAM-1 blocking antibodies attenuated MMP production in direct contact to that observed in the indirect. Heparin introduction achieved a similar outcome. Conclusions ICAM-1-CD43 interaction plays a vital role in tumor cells-peritoneum adhesion and invasion, which is manifested by the increased production of MMPs leading to tumor invasion and peritoneal loco-regional. Blocking this interaction with heparin can provide a new therapeutic option.

scholarly journals The Role of Metabolism in Tumor Immune Evasion: Novel Approaches to Improve Immunotherapy

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 361
Author(s):  
Alberto Cruz-Bermúdez ◽  
Raquel Laza-Briviesca ◽  
Marta Casarrubios ◽  
Belén Sierra-Rodero ◽  
Mariano Provencio
Keyword(s):  
Tumor Cells ◽  
Immune Evasion ◽  
Building Materials ◽  
Cell Types ◽  
First Line ◽  
Tumor Immune Evasion ◽  
Novel Approaches ◽  
Metabolic Properties ◽  
Selection Of

The tumor microenvironment exhibits altered metabolic properties as a consequence of the needs of tumor cells, the natural selection of the most adapted clones, and the selfish relationship with other cell types. Beyond its role in supporting uncontrolled tumor growth, through energy and building materials obtention, metabolism is a key element controlling tumor immune evasion. Immunotherapy has revolutionized the treatment of cancer, being the first line of treatment for multiple types of malignancies. However, many patients either do not benefit from immunotherapy or eventually relapse. In this review we overview the immunoediting process with a focus on the metabolism-related elements that are responsible for increased immune evasion, either through reduced immunogenicity or increased resistance of tumor cells to the apoptotic action of immune cells. Finally, we describe the main molecules to modulate these immune evasion processes through the control of the metabolic microenvironment as well as their clinical developmental status.

scholarly journals Human platelets exert cytotoxic effects on tumor cells

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1252-1255 ◽  
Author(s):  
GM Ibele ◽  
NE Kay ◽  
GJ Johnson ◽  
HS Jacob
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Types ◽  
Human Platelets ◽  
Fixed Number ◽  
Cell Cytotoxicity ◽  
Lipoxygenase Inhibitor ◽  
Tumor Metastases

Abstract Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.

scholarly journals Regulator of calcineurin 1 gene isoform 4 in pancreatic ductal adenocarcinoma regulates the progression of tumor cells

Oncogene ◽  
2021 ◽  
Author(s):  
Mengyi Lao ◽  
Xiaozhen Zhang ◽  
Tao Ma ◽  
Jian Xu ◽  
Hanshen Yang ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Vital Role ◽  
Ductal Adenocarcinoma ◽  
Migration And Invasion ◽  
Metastasis Model ◽  
Inducible Protein

AbstractTherapeutic strategies to treat pancreatic ductal adenocarcinoma (PDAC) remain unsatisfying and limited. Therefore, it is imperative to fully determine the mechanisms underlying PDAC progression. In the present study, we report a novel role of regulator of calcineurin 1, isoform 4 (RCAN1.4) in regulating PDAC progression. We demonstrated that RCAN1.4 expression was decreased significantly in PDAC tissues compared with that in para-cancerous tissues, and correlated with poor prognosis of patients with pancreatic cancer. In vitro, stable high expression of RCAN1.4 could suppress the metastasis and proliferation and angiogenesis of pancreatic tumor cells. In addition, interferon alpha inducible protein 27 (IFI27) was identified as having a functional role in RCAN1.4-mediated PDAC migration and invasion, while VEGFA play a vital role in RCAN1.4-mediated PDAC angiogenesis. Analysis of mice with subcutaneously/orthotopic implanted xenograft tumors and liver metastasis model confirmed that RCAN1.4 could modulate the growth, metastasis, and angiogenesis of tumors via IFI27/VEGFA in vivo. In conclusion, our results suggested that RCAN1.4 suppresses the growth, metastasis, and angiogenesis of PDAC, functioning partly via IFI27 and VEGFA. Importantly, our results provided possible diagnostic criteria and therapeutic targets for PDAC.

scholarly journals Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural Insights from a Computational Model

2020 ◽  
Author(s):  
Junho Lee ◽  
Donggu Lee ◽  
Sean Lawler ◽  
Yangjin Kim
Keyword(s):  
Mathematical Model ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Tumor Invasion ◽  
Neutrophil Extracellular Traps ◽  
Tumor Cell Invasion ◽  
Invasion And Metastasis ◽  
Extracellular Traps ◽  
Tumor Associated Neutrophils

AbstractLung cancer is one of the leading causes of cancer-related deaths worldwide and is characterized by hijacking immune system for active growth and aggressive metastasis. Neutrophils, which in their original form should establish immune activities to the tumor as a first line of defense, are undermined by tumor cells to promote tumor invasion in several ways. In this study, we investigate the mutual interactions between the tumor cells and the neutrophils that facilitate tumor invasion by developing a mathematical model that involves taxis-reaction-diffusion equations for the critical components in the interaction. These include the densities of tumor and neutrophils, and the concentrations of signaling molecules and structure such as neutrophil extracellular traps (NETs). We apply the mathematical model to a Boyden invasion assay used in the experiments to demonstrate that the tumor-associated neutrophils can enhance tumor cell invasion by secreting the neutrophil elastase. We show that the model can both reproduce the major experimental observation on NET-mediated cancer invasion and make several important predictions to guide future experiments with the goal of the development of new anti-tumor strategies. Moreover, using this model, we investigate the fundamental mechanism of NET-mediated invasion of cancer cells and the impact of internal and external heterogeneity on the migration patterning of tumour cells and their response to different treatment schedules.Author summaryWhen cancer patients are diagnosed with tumours at a primary site, the cancer cells are often found in the blood or already metastasized to the secondary sites in other organs. These metastatic cancer cells are more resistant to major anti-cancer therapies, and lead to the low survival probability. Until recently, the role of neutrophils, specifically tumor-associated neutrophils as a member of complex tumor microenvironment, has been ignored for a long time due to technical difficulties in tumor biology but these neutrophils are emerging as an important player in regulation of tumor invasion and metastasis. The mutual interaction between a tumor and neutrophils from bone marrow or in blood induces the critical transition of the naive form, called the N1 type, to the more aggressive phenotype, called the N2 TANs, which then promotes tumor invasion. In this article, we investigate how stimulated neutrophils with different N1 and N2 landscapes shape the metastatic potential of the lung cancers. Our simulation framework is designed for boyden invasion chamber in experiments and based on a mathematical model that describes how tumor cells interact with neutrophils and N2 TANs can promote tumor cell invasion. We demonstrate that the efficacy of anti-tumor (anti-invasion) drugs depend on this critical communication and N1 → N2 landscapes of stimulated neutrophils.

scholarly journals The Emerging Role of the Microenvironment in Endometrial Cancer

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 408 ◽  
Author(s):  
Subhransu Sahoo ◽  
Xu Zhang ◽  
Hubert Hondermarck ◽  
Pradeep Tanwar
Keyword(s):  
Endometrial Cancer ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Cancer Recurrence ◽  
Metastatic Potential ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Signaling Cascades ◽  
Metastatic Progression

Endometrial cancer (EC) is one of the most frequently diagnosed cancers in women, and despite recent therapeutic advances, in many cases, treatment failure results in cancer recurrence, metastasis, and death. Current research demonstrates that the interactive crosstalk between two discrete cell types (tumor and stroma) promotes tumor growth and investigations have uncovered the dual role of the stromal cells in the normal and cancerous state. In contrast to tumor cells, stromal cells within the tumor microenvironment (TME) are genetically stable. However, tumor cells modify adjacent stromal cells in the TME. The alteration in signaling cascades of TME from anti-tumorigenic to pro-tumorigenic enhances metastatic potential and/or confers therapeutic resistance. Therefore, the TME is a fertile ground for the development of novel therapies. Furthermore, disrupting cancer-promoting signals from the TME or re-educating stromal cells may be an effective strategy to impair metastatic progression. Here, we review the paradoxical role of different non-neoplastic stromal cells during specific stages of EC progression. We also suggest that the inhibition of microenvironment-derived signals may suppress metastatic EC progression and offer novel potential therapeutic interventions.

scholarly journals Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies

2020 ◽  
Vol 21 (19) ◽  
pp. 7371
Author(s):  
Maria Peleli ◽  
Aristidis Moustakas ◽  
Andreas Papapetropoulos
Keyword(s):  
Tumor Cells ◽  
Cell Types ◽  
Cell Interaction ◽  
Intermediate Cell ◽  
Pharmacological Interventions ◽  
New Therapeutic Approaches ◽  
Antiangiogenic Therapies ◽  
Mechanisms Of Formation ◽  
Cns Malignancies

Glioblastoma and other brain or CNS malignancies (like neuroblastoma and medulloblastoma) are difficult to treat and are characterized by excessive vascularization that favors further tumor growth. Since the mean overall survival of these types of diseases is low, the finding of new therapeutic approaches is imperative. In this review, we discuss the importance of the interaction between the endothelium and the tumor cells in brain and CNS malignancies. The different mechanisms of formation of new vessels that supply the tumor with nutrients are discussed. We also describe how the tumor cells (TC) alter the endothelial cell (EC) physiology in a way that favors tumorigenesis. In particular, mechanisms of EC–TC interaction are described such as (a) communication using secreted growth factors (i.e., VEGF, TGF-β), (b) intercellular communication through gap junctions (i.e., Cx43), and (c) indirect interaction via intermediate cell types (pericytes, astrocytes, neurons, and immune cells). At the signaling level, we outline the role of important mediators, like the gasotransmitter nitric oxide and different types of reactive oxygen species and the systems producing them. Finally, we briefly discuss the current antiangiogenic therapies used against brain and CNS tumors and the potential of new pharmacological interventions that target the EC–TC interaction.

scholarly journals Development, Diversity, and Neurogenic Capacity of Enteric Glia

2022 ◽  
Vol 9 ◽  
Author(s):  
Werend Boesmans ◽  
Amelia Nash ◽  
Kinga R. Tasnády ◽  
Wendy Yang ◽  
Lincon A. Stamp ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Glial Cells ◽  
Cell Types ◽  
Vital Role ◽  
Enteric Neurons ◽  
Enteric Glia ◽  
Enteric Glial Cells ◽  
Functional Versatility

Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the “support” cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They mediate enteric nervous system signalling and play a vital role in the local regulation of gut functions. Enteric glial cells interact with other gastrointestinal cell types such as those of the epithelium and immune system to preserve homeostasis, and are perceptive to luminal content. Their functional versatility and phenotypic heterogeneity are mirrored by an extensive level of plasticity, illustrated by their reactivity in conditions associated with enteric nervous system dysfunction and disease. As one of the hallmarks of their plasticity and extending their operative relationship with enteric neurons, enteric glia also display neurogenic potential. In this review, we focus on the development of enteric glial cells, and the mechanisms behind their heterogeneity in the adult gut. In addition, we discuss what is currently known about the role of enteric glia as neural precursors in the enteric nervous system.

scholarly journals Human platelets exert cytotoxic effects on tumor cells

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1252-1255
Author(s):  
GM Ibele ◽  
NE Kay ◽  
GJ Johnson ◽  
HS Jacob
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Types ◽  
Human Platelets ◽  
Fixed Number ◽  
Cell Cytotoxicity ◽  
Lipoxygenase Inhibitor ◽  
Tumor Metastases

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.

Tunneling Nanotubes: A Versatile Target for Cancer Therapy

2018 ◽  
Vol 18 (6) ◽  
pp. 514-521 ◽  
Author(s):  
Pragyaparamita Sahu ◽  
Soumya Ranjan Jena ◽  
Luna Samanta
Keyword(s):  
Tumor Invasion ◽  
Cell Types ◽  
Tumor Formation ◽  
Malignant Cells ◽  
Intercellular Bridge ◽  
Cell Organelles ◽  
Tunneling Nanotubes ◽  
Development Of Resistance ◽  
Cell Cell

Currently Cancer is the leading cause of death worldwide. Malignancy or cancer is a class of diseases characterized by uncontrolled cell growth that eventually invade other tissues and develop secondary malignant growth at other sites by metastasis. Intercellular communication plays a major role in cancer, particularly in the process of cell proliferation and coordination which in turn leads to tumor invasion, metastasis and development of resistance to therapy. Cells communicate among themselves in a variety of ways, namely: i) via gap junctions with adjacent cells; ii) via exosomes with nearby cells; and iii) via chemical messengers with distant cells. Besides, cell - cell connection by tunneling nanotubes (TnTs) is recently gaining importance where intercellular components are transferred between cells. In general cell organelles like Golgi vesicle and mitochondria; and biomolecules like nucleic acids and proteins are transferred through these TnTs. These TnTs are long cytoplasmic extensions made up of actin that function as intercellular bridge and connect a wide variety of cell types. Malignant cells form TnTs with either other malignant cells or cells of the surrounding tumor matrix. These TnTs help in the process of initiation of tumor formation, its organization and propagation. The current review focuses on the role of TnTs mediated cell – cell signaling in cancer micro-environment. Drugs that inhibit TnT-formation such as metformin and everolimus can be targeted towards TnTs in the management of cancer growth, proliferation, tumor invasion and metastasis.

Sign in / Sign up

Export Citation Format

Share Document