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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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An Emerging Model for Cancer Development from a Tumor Microenvironment Perspective in Mice and Humans.

Ryuji Yamaguchi1, Guy Perkins2

  • 1JRC, Medical Research Company, Osaka, Japan. rudy.yamaguchi@hushmail.com.

Advances in Experimental Medicine and Biology
|February 8, 2020
PubMed
Summary

This study introduces a new cancer development model where the tumor microenvironment (TME) is central. It details five stages, from colonization to metastasis, emphasizing the TME

Keywords:
Cancer associated fibroblast (CAF)Cancer developmentChemokinesCytokinesDuctal carcinoma in situ (DCIS)Epithelial-to-mesenchymal transition (EMT)Lymphocytic infiltrationMalignant pleural mesothelioma (MPN)MetastasisMyeloid-derived suppressor cell (MDSC)Natural killer cell (NK)Pleural effusionTumor associated macrophage (TAM)Tumor microenvironment

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Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Traditional cancer development models focus on genetic mutations within cancer cells.
  • An emerging paradigm highlights the critical role of the tumor microenvironment (TME) in cancer progression.

Purpose of the Study:

  • To present and examine an emerging model of cancer development centered on the tumor microenvironment (TME).
  • To explore the dynamic interplay between cancer cells and their TME across distinct developmental stages.
  • To evaluate clinical and animal data supporting this TME-centric cancer development model.

Main Methods:

  • Review of clinical findings and animal experiments related to cancer development.
  • Analysis of a five-stage model of cancer progression: colonization, lymphocyte infiltration, silenced tumor, epithelial-to-mesenchymal transition (EMT), and metastasis.
  • Examination of the bidirectional influence between cancer cells and the TME, including immune evasion and cytokine signaling.

Main Results:

  • Cancer development progresses through five stages, each characterized by specific interactions within the TME.
  • The TME significantly influences cancer cell behavior, including immune evasion (e.g., by natural killer (NK) cells) and metastasis.
  • Cancer cells, in turn, actively shape their TME, creating a complex feedback loop.

Conclusions:

  • The tumor microenvironment (TME) plays an integral role in cancer development, challenging purely genetic mutation-based models.
  • This TME-centric model provides a framework for understanding cancer progression from initial colonization to distant metastasis.
  • Further research is warranted to determine the extent to which the TME governs specific aspects of cancer development.