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In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
The Role of Tumor Associated Macrophages (TAMs) in Cancer Progression, Chemoresistance, Angiogenesis and Metastasis -
Siva Dallavalasa1, Narasimha M Beeraka1, Chaithanya G Basavaraju1
1Center 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.
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.
Insights
Tumor-associated macrophages (TAMs) promote cancer progression, angiogenesis, and metastasis. Targeting TAMs with phytomedicines and multi-omics approaches offers novel therapeutic strategies against cancer.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) significantly influence cancer cell survival, progression, and immune suppression.
- TAMs contribute to angiogenesis, metastasis, and multidrug resistance by producing various mediators.
- TAMs exhibit plastic differentiation states, responding to local cues and influencing cancer progression.
Purpose of the Study:
- To discuss the multifaceted role of TAMs in tumor progression, angiogenesis, and metastasis.
- To explore signaling cascades regulated by TAMs that contribute to chemoresistance.
- To highlight the potential of phytomedicines and natural products as adjunct therapies targeting TAMs.
Main Methods:
- Review of existing literature on TAMs' role in cancer.
- Discussion of epigenetic regulation of macrophage polarization (M1/M2).
- Exploration of signaling pathways involved in TAM-mediated chemoresistance.
Main Results:
- TAMs are key drivers of tumor progression, angiogenesis, and metastasis.
- Epigenetic mechanisms regulate TAM polarization, offering therapeutic targets.
- Phytomedicines show promise in overcoming TAM-induced chemoresistance.
Conclusions:
- Targeting TAMs is a promising strategy for cancer therapy.
- Phytomedicines and natural products can be utilized as adjunct therapeutics.
- Multi-omics approaches are crucial for developing novel TAM-targeting therapies.
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