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.
