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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
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  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Medical Microbiology
  9. Medical Infection Agents (incl. Prions)
  11. Less Severe Tumor Growth In Mice In Which Mgmt Is Conditionally Deleted Using The Lysm-cre System, And The Possible Impacts Of Dna Methylation In Tumor-associated Macrophages.
  1. Home
  3. Research Domains
  5. Biomedical And Clinical Sciences
  7. Medical Microbiology
  9. Medical Infection Agents (incl. Prions)
  11. Less Severe Tumor Growth In Mice In Which Mgmt Is Conditionally Deleted Using The Lysm-cre System, And The Possible Impacts Of Dna Methylation In Tumor-associated Macrophages.

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Less severe tumor growth in mice in which mgmt is conditionally deleted using the LysM-Cre system, and the possible impacts of DNA methylation in tumor-associated macrophages.

Pornpimol Phuengmaung1,2, Wilasinee Saisorn1,2, Atsadang Boonmee3

  • 1Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

International Immunology
|June 11, 2025

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
cancerepigenetics

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The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is crucial for tumor-associated macrophage (TAM) function. Without MGMT, TAMs are less abundant, hindering cancer growth, suggesting MGMT inhibitors as a cancer therapy.

Area of Science:

  • Immunology
  • Cancer Biology
  • DNA Repair

Background:

  • O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme vital in cancer cells.
  • The role of MGMT in macrophages, particularly in the tumor microenvironment, remains largely unexplored.

Purpose of the Study:

  • To investigate the impact of MGMT on macrophage polarization and function.
  • To determine the role of MGMT in tumor-associated macrophage (TAM) mediated tumor growth.

Main Methods:

  • Utilized MGMT-deficient (null) mice and wild-type littermate controls for in vivo tumor studies with MC38 colon cancer cells.
  • Isolated bone marrow-derived macrophages and polarized them into M1, M2, and TAM phenotypes in vitro.
  • Assessed macrophage polarization, pro-inflammatory/M2 markers, tumoricidal activity, cellular respiration, oxidative stress, and DNA damage.

Main Results:

  • MGMT was upregulated in activated macrophages (M1, M2, TAM), most prominently in M1.
  • MGMT-null macrophages exhibited impaired M1 pro-inflammation and M2 polarization.
  • MGMT-null M1 macrophages showed reduced tumoricidal activity compared to controls.
  • TAMs from MGMT-null mice displayed reduced respiration, increased cell injury, oxidative stress, and DNA breaks.

Conclusions:

  • TAM transformation requires cellular energy and induces DNA damage, necessitating MGMT for repair.
  • Absence of MGMT significantly reduces TAM abundance, thereby inhibiting cancer progression.
  • Targeting MGMT with inhibitors presents a promising therapeutic strategy for various cancers.