The Role of Tumor Associated Macrophages (TAMs) in Cancer Progression, Chemoresistance, Angiogenesis and Metastasis - Current Status

2021 ◽  
Vol 28 ◽  
Author(s):  
Gjumrakch Aliev ◽  
Siva Dallavalasa ◽  
Narasimha M. Beeraka ◽  
Chaithanya G. Basavaraju ◽  
Subba Rao V. Tulimilli ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Macrophage Polarization ◽  
Chemotherapeutic Agents ◽  
Current Status ◽  
Tumor Associated Macrophages ◽  
Metastatic Behavior ◽  
Cancer Cell Survival ◽  
Pleiotropic Properties

: Tumor associated macrophages (TAMs), located in the tumor microenvironment (TME), play a significant role in cancer cell survival and progression. TAMs have been involved in producing immuno-suppressive TME in the tumor by generating inflammatory mediators, growth factors, cytokines, chemokines, etc. TAMs can influence the angiogenesis, metastatic behavior of tumor cells (TCs) and cause multidrug resistance. TAMs within the TME can enhance cancer cell metastasis and are stromal and perivascular. The angiogenesis is promoted at the hypoxia, and the avascular zones of TME. Differentiation states of TAMs are considered ‘plastic’ as they exhibit temporal expression of one or several phenotypes depending on local cues. Emerging cancer research depicted the epigenetic regulation of macrophage polarization (both M1s, M2s) and their potential implications to develop pharmacologic modulators and microRNAs to act as molecular switches and even to serve as targeted therapies to inhibit tumor growth. In the present article, the role of TAMs in tumor progression, angiogenesis and metastasis was discussed. In addition, key signaling cascades regulated by TAMs, which have a role in chemoresistance, were also discussed. Currently, novel pleiotropic properties of various anticancer phytomedicines are gaining importance as they assist in overcoming TAMs-induced chemoresistance. Moreover, these phytomedicines are being tested as ‘adjunct therapeutics’ along with chemotherapeutic agents, anti-angiogenic molecules, anti-metastatic compounds, and other immune-checkpoint blockers against tumor metastasis/angiogenesis. Hence, a brief note on natural products targeting TAMs was provided. In summary, this review would benefit pharmacologists and medical professionals to develop therapies to target TAMs using multi-OMICs approaches, including genomics, epigenomics, transcriptomics, and proteomics.

scholarly journals mTOR Complexes as a Nutrient Sensor for Driving Cancer Progression

2018 ◽  
Vol 19 (10) ◽  
pp. 3267 ◽  
Author(s):  
Mio Harachi ◽  
Kenta Masui ◽  
Yukinori Okamura ◽  
Ryota Tsukui ◽  
Paul Mischel ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Cancer Cell Survival

Recent advancement in the field of molecular cancer research has clearly revealed that abnormality of oncogenes or tumor suppressor genes causes tumor progression thorough the promotion of intracellular metabolism. Metabolic reprogramming is one of the strategies for cancer cells to ensure their survival by enabling cancer cells to obtain the macromolecular precursors and energy needed for the rapid growth. However, an orchestration of appropriate metabolic reactions for the cancer cell survival requires the precise mechanism to sense and harness the nutrient in the microenvironment. Mammalian/mechanistic target of rapamycin (mTOR) complexes are known downstream effectors of many cancer-causing mutations, which are thought to regulate cancer cell survival and growth. Recent studies demonstrate the intriguing role of mTOR to achieve the feat through metabolic reprogramming in cancer. Importantly, not only mTORC1, a well-known regulator of metabolism both in normal and cancer cell, but mTORC2, an essential partner of mTORC1 downstream of growth factor receptor signaling, controls cooperatively specific metabolism, which nominates them as an essential regulator of cancer metabolism as well as a promising candidate to garner and convey the nutrient information from the surrounding environment. In this article, we depict the recent findings on the role of mTOR complexes in cancer as a master regulator of cancer metabolism and a potential sensor of nutrients, especially focusing on glucose and amino acid sensing in cancer. Novel and detailed molecular mechanisms that amino acids activate mTOR complexes signaling have been identified. We would also like to mention the intricate crosstalk between glucose and amino acid metabolism that ensures the survival of cancer cells, but at the same time it could be exploitable for the novel intervention to target the metabolic vulnerabilities of cancer cells.

scholarly journals Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Christina Mertens ◽  
Matthias Schnetz ◽  
Claudia Rehwald ◽  
Stephan Grein ◽  
Eiman Elwakeel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Lipocalin 2 ◽  
Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

scholarly journals Role of Sigma-1 Receptor in Calcium Modulation: Possible Involvement in Cancer

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 139
Author(s):  
Ilaria Pontisso ◽  
Laurent Combettes
Keyword(s):  
Cell Survival ◽  
Cancer Progression ◽  
Strong Impact ◽  
Protective Function ◽  
Sigma 1 Receptor ◽  
Contact Sites ◽  
Calcium Modulation ◽  
Sigma 1 ◽  
Cancer Cell Survival

Ca2+ signaling plays a pivotal role in the control of cellular homeostasis and aberrant regulation of Ca2+ fluxes have a strong impact on cellular functioning. As a consequence of this ubiquitous role, Ca2+ signaling dysregulation is involved in the pathophysiology of multiple diseases including cancer. Indeed, multiple studies have highlighted the role of Ca2+ fluxes in all the steps of cancer progression. In particular, the transfer of Ca2+ at the ER-mitochondrial contact sites, also known as mitochondrial associated membranes (MAMs), has been shown to be crucial for cancer cell survival. One of the proteins enriched at this site is the sigma-1 receptor (S1R), a protein that has been described as a Ca2+-sensitive chaperone that exerts a protective function in cells in various ways, including the modulation of Ca2+ signaling. Interestingly, S1R is overexpressed in many types of cancer even though the exact mechanisms by which it promotes cell survival are not fully elucidated. This review summarizes the findings describing the roles of S1R in the control of Ca2+ signaling and its involvement in cancer progression.

scholarly journals The Role of Platelet-Derived ADP and ATP in Promoting Pancreatic Cancer Cell Survival and Gemcitabine Resistance

Cancers ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 142 ◽  
Author(s):  
Omar Elaskalani ◽  
Marco Falasca ◽  
Niamh Moran ◽  
Michael Berndt ◽  
Pat Metharom
Keyword(s):  
Pancreatic Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Gemcitabine Resistance ◽  
Cancer Cell Survival

The role of microvesicles in cancer progression and drug resistance

2013 ◽  
Vol 41 (1) ◽  
pp. 293-298 ◽  
Author(s):  
Samireh Jorfi ◽  
Jameel M. Inal
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Progression ◽  
Chemotherapeutic Agents ◽  
Malignant Cells ◽  
Intercellular Transport ◽  
Wide Range ◽  
Anti Cancer ◽  
Mdr Multidrug Resistance

Microvesicles are shed constitutively, or upon activation, from both normal and malignant cells. The process is dependent on an increase in cytosolic Ca2+, which activates different enzymes, resulting in depolymerization of the actin cytoskeleton and release of the vesicles. Drug resistance can be defined as the ability of cancer cells to survive exposure to a wide range of anti-cancer drugs, and anti-tumour chemotherapeutic treatments are often impaired by innate or acquired MDR (multidrug resistance). Microvesicles released upon chemotherapeutic agents prevent the drugs from reaching their targets and also mediate intercellular transport of MDR proteins.

scholarly journals Differing Roles of Hyaluronan Molecular Weight on Cancer Cell Behavior and Chemotherapy Resistance

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 482 ◽  
Author(s):  
Zoe Price ◽  
Noor Lokman ◽  
Carmela Ricciardelli
Keyword(s):  
Molecular Weight ◽  
Tyrosine Kinase ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Receptor Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Therapy Resistance ◽  
Cell Behavior ◽  
Mesenchymal Transition

Hyaluronan (HA), a glycosaminoglycan located in the extracellular matrix, is important in embryo development, inflammation, wound healing and cancer. There is an extensive body of research demonstrating the role of HA in all stages of cancer, from initiation to relapse and therapy resistance. HA interacts with multiple cell surface receptors, including CD44, receptor for hyaluronan mediated motility (RHAMM) and intracellular signaling pathways, including receptor tyrosine kinase pathways, to promote the survival and proliferation of cancer cells. Additionally, HA promotes the formation of cancer stem cell (CSC) populations, which are hypothesized to be responsible for the initiation of tumors and therapy resistance. Recent studies have identified that the molecular weight of HA plays differing roles on both normal and cancer cell behavior. This review explores the role of HA in cancer progression and therapy resistance and how its molecular weight is important in regulating CSC populations, epithelial to mesenchymal transition (EMT), ATP binding cassette (ABC) transporter expression and receptor tyrosine kinase pathways.

scholarly journals Dual Role of Autophagy in Colon Cancer Cell Survival

2011 ◽  
Vol 18 (S3) ◽  
pp. 239-239 ◽  
Author(s):  
Shi Yu Yang ◽  
Marc C. Winslet
Keyword(s):  
Colon Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Dual Role ◽  
Colon Cancer Cell ◽  
Cancer Cell Survival

scholarly journals Active regulator of SIRT1 is required for cancer cell survival but not for SIRT1 activity

Open Biology ◽  
2013 ◽  
Vol 3 (11) ◽  
pp. 130130 ◽  
Author(s):  
John R. P. Knight ◽  
Simon J. Allison ◽  
Jo Milner
Keyword(s):  
Cell Survival ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Survival ◽  
Cancer Cell Lines ◽  
Cellular Processes ◽  
Disease States ◽  
Cancer Cell Survival ◽  
P53 Activation

The NAD + -dependent deacetylase SIRT1 is involved in diverse cellular processes, and has also been linked with multiple disease states. Among these, SIRT1 expression negatively correlates with cancer survival in both laboratory and clinical studies. Active regulator of SIRT1 (AROS) was the first reported post-transcriptional regulator of SIRT1 activity, enhancing SIRT1-mediated deacetylation and downregulation of the SIRT1 target p53. However, little is known regarding the role of AROS in regulation of SIRT1 during disease. Here, we report the cellular and molecular effects of RNAi-mediated AROS suppression, comparing this with the role of SIRT1 in a panel of human cell lines of both cancerous and non-cancerous origins. Unexpectedly, AROS is found to vary in its modulation of p53 acetylation according to cell context. AROS suppresses p53 acetylation only following the application of cell damaging stress, whereas SIRT1 suppresses p53 under all conditions analysed. This supplements the original characterization of AROS but indicates that SIRT1 activity can persist following suppression of AROS. We also demonstrate that knockdown of AROS induces apoptosis in three cancer cell lines, independent of p53 activation. Importantly, AROS is not required for the viability of three non-cancer cell lines indicating a putative role for AROS in specifically promoting cancer cell survival.

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