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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
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Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...

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A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication
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Published on: September 20, 2016

Organ-Specific Cancer-Associated Fibroblast Subtypes Across the Digestive System Linked to Cancer Hallmarks.

Huaitao Wang1,2,3, Takashi Semba1, Atsuko Yonemura1

  • 1Division of Carcinogenesis, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.

Cancer Science
|June 1, 2026
PubMed
Summary

Cancer-associated fibroblasts (CAFs) exhibit subtypes influencing gastrointestinal cancer outcomes. Myofibroblastic CAFs correlate with poor prognosis, while inflammatory CAFs are linked to better outcomes and anti-tumor immunity.

Keywords:
cancer‐associated fibroblastsgastrointestinal cancerpatient prognosissingle‐cell RNA sequencingspatial transcriptomics

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Assessment of Mitochondrial Health in Cancer-Associated Fibroblasts Isolated from 3D Multicellular Lung Tumor Spheroids

Published on: October 21, 2022

Area of Science:

  • Oncology
  • Immunology
  • Bioinformatics

Background:

  • Cancer-associated fibroblasts (CAFs) are key players in the tumor microenvironment (TME) of gastrointestinal (GI) cancers, impacting progression, immunity, and treatment resistance.
  • The heterogeneity, tissue specificity, and clinical significance of CAFs across diverse GI cancers are not fully understood.

Purpose of the Study:

  • To define CAF subtypes within GI cancers using integrated single-cell RNA sequencing data.
  • To assess the prognostic value and functional characteristics of identified CAF subtypes in a large patient cohort.

Main Methods:

  • Integration of 14 single-cell RNA-sequencing datasets (239 GI adenocarcinoma samples).
  • Machine learning-based deconvolution of 18 bulk transcriptomic cohorts (3396 patients) to estimate CAF subtype abundance.
  • Analysis of functional states, differentiation, cell-cell communication, and spatial organization using various computational and transcriptomic techniques.

Main Results:

  • Identification of eight distinct CAF subtypes with organ-specific distributions.
  • Two myofibroblastic CAF subtypes (myCAF1, myCAF2) associated with poor prognosis, linked to ECM remodeling, TGF-β signaling, hypoxia, and immunosuppressive crosstalk.
  • Inflammatory CAF subtype 1 (iCAF1) associated with favorable prognosis and enhanced anti-tumor immune cell infiltration.
  • Spatial transcriptomics revealed distinct spatial localization of CAF subtypes within the GI TME.

Conclusions:

  • CAF functional states and spatial context are critical determinants of GI cancer progression and patient outcomes.
  • myCAF-driven niches promote immune suppression and unfavorable prognosis.
  • A balanced inflammatory CAF program may foster anti-tumor immunity.