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The Tumor Microenvironment

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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MAME Models for 4D Live-cell Imaging of Tumor: Microenvironment Interactions that Impact Malignant Progression

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Published on: February 17, 2012

Challenges and Opportunities Modeling the Dynamic Tumor Matrisome.

Shelly R Peyton¹, Manu O Platt², Edna Cukierman³

¹Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, MA, USA.

|October 18, 2023

Summary

Targeting cancer metastasis requires understanding the tumor microenvironment, specifically the dynamic interplay between cancer-associated fibroblasts (CAFs) and their self-generated extracellular matrix (ECM), termed the "tumor matrisome". Studying this CAF/ECM unit offers new avenues for personalized cancer medicine.

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Area of Science:

Oncology
Biomedical Engineering
Cancer Biology

Background:

Cancer metastasis is complex, with specific tissues supporting tumor growth due to factors like the extracellular matrix (ECM).
Traditional research focused on tumor cells in 2D cultures, but intravital imaging reveals real-time tumor cell dynamics.
The dynamic nature of the interstitial ECM in the tumor microenvironment necessitates advanced in vitro models.

Purpose of the Study:

To highlight the critical role of cancer-associated fibroblasts (CAFs) and their self-generated ECM (the tumor matrisome) in supporting metastatic disease.
To discuss the challenges and opportunities in modeling the dynamic CAF/ECM unit.
To explore how understanding tumor matrisome remodeling can inform novel therapeutic strategies.

Main Methods:

Focuses on a perspective review of existing research and emerging techniques.
Highlights the use of intravital imaging and advanced in vitro controlled environments.
Discusses the role of ECM proteases in tumor matrisome remodeling.

Main Results:

Identifies CAFs and their self-generated ECM as key players in maintaining the tumor microenvironment's pathological homeostasis.
Emphasizes the limitations of 2D culture models for studying dynamic ECM interactions.
Suggests that understanding tumor matrisome dynamics is crucial for developing new therapeutic approaches.

Conclusions:

Modeling the dynamic CAF/ECM unit presents significant challenges and opportunities for cancer research.
The tumor matrisome, including CAF-generated ECM and secreted factors, is a critical component of the tumor microenvironment.
Insights into tumor matrisome dynamics may pave the way for personalized medicine strategies beyond genomics.