Abstract
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.
Keywords: Tumor associated macrophages, tumor microenvironment, chemosensitization, tumor angiogenesis, M1 and M2, macrophages, natural products.
Current Medicinal Chemistry
Title:The Role of Tumor Associated Macrophages (TAMs) in Cancer Progression, Chemoresistance, Angiogenesis and Metastasis - Current Status
Volume: 28 Issue: 39
Author(s): Siva Dallavalasa, Narasimha M. Beeraka, Chaithanya G. Basavaraju, SubbaRao V. Tulimilli, Surya Prabha Sadhu, Konathala Rajesh, Gjumrakch Aliev and SubbaRao V. Madhunapantula*
Affiliation:
- Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education & Research (JSS AHER), Mysuru 570015, Karnataka,India
Keywords: Tumor associated macrophages, tumor microenvironment, chemosensitization, tumor angiogenesis, M1 and M2, macrophages, natural products.
Abstract: 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.
Export Options
About this article
Cite this article as:
Dallavalasa Siva , Beeraka M. Narasimha , Basavaraju G. Chaithanya , Tulimilli V. SubbaRao , Sadhu Prabha Surya , Rajesh Konathala , Aliev Gjumrakch and Madhunapantula V. SubbaRao *, The Role of Tumor Associated Macrophages (TAMs) in Cancer Progression, Chemoresistance, Angiogenesis and Metastasis - Current Status, Current Medicinal Chemistry 2021; 28 (39) . https://dx.doi.org/10.2174/0929867328666210720143721
DOI https://dx.doi.org/10.2174/0929867328666210720143721 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Positron Emission Tomography and Computer Tomography (PET/CT) in Prostate, Bladder, and Testicular Cancers
Current Medicinal Chemistry From Body Art to Anticancer Activities: Perspectives on Medicinal Properties of Henna
Current Drug Targets Targeting Synthetic Lethality in DNA Damage Repair Pathways as an Anti-Cancer Strategy
Current Drug Targets RNA Interference-Mediated Validation of Survivin and Apollon/BRUCE as New Therapeutic Targets for Cancer Therapy
Current Topics in Medicinal Chemistry Regulation of Expression and Function of IDO in Human Dendritic Cells
Current Medicinal Chemistry Editorial (Thematic Issue: “miRNA and Cancer; Computational and Experimental Approaches”)
Current Pharmaceutical Biotechnology Genistein Inhibits Cell Growth and Induces Apoptosis Through Up-regulation of miR-34a in Pancreatic Cancer Cells
Current Drug Targets Promising Strategies for Overcoming BRAF Inhibitor Resistance Based on Known Resistance Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Manganese Superoxide Dismutase (Sod2) and Redox-Control of Signaling Events That Drive Metastasis
Anti-Cancer Agents in Medicinal Chemistry VEGF Signal System: The Application of Antiangiogenesis
Current Medicinal Chemistry Characterization of Particulate Drug Delivery Systems for Oral Delivery of Peptide and Protein Drugs
Current Pharmaceutical Design The Past, Current Studies and Future of Organometallic <sup>99m</sup>Tc(CO)3 Labeled Peptides and Proteins
Current Pharmaceutical Design Organosulfur Compounds in Cancer Chemoprevention
Mini-Reviews in Medicinal Chemistry Ternary Copper (II) Complex Induced Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Current Phthalocyanines Delivery Systems in Photodynamic Therapy: An Updated Review
Current Medicinal Chemistry Cervical Cancer Diagnosis: Insights into Biochemical Biomarkers and Imaging Techniques
Combinatorial Chemistry & High Throughput Screening Roles of Calcium and Tyrosine Kinases in the Pathogenesis of Type 2 Diabetes Mellitus
Current Enzyme Inhibition Recent Advances in Azo Dye Degrading Enzyme Research
Current Protein & Peptide Science Is the Vagina an Adequate Route for the Administration of Hormonal Contraceptives?
Current Drug Metabolism VEGF in Tumor Progression and Targeted Therapy
Current Cancer Drug Targets