Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment Research

Background:

• Tumor metastasis is a key factor in poor cancer prognosis.
• Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment (TME).
• CAFs play critical roles in regulating tumor metastasis.

Purpose of the Study:

• To systematically review CAF roles in eight stages of tumor dissemination.
• To explore CAF involvement in ECM remodeling, EMT, angiogenesis, metabolism, migration, immune escape, dormancy, and PMN formation.
• To compile therapeutic strategies targeting CAFs for anti-metastatic treatments.

Main Methods:

• Systematic literature review.
• Analysis of CAF functions across distinct metastatic stages.
• Compilation of current CAF-targeting therapeutic approaches.

Main Results:

• CAFs influence extracellular matrix remodeling, promoting tumor cell invasion.
• CAFs facilitate epithelial-mesenchymal transition (EMT), enhancing cell motility.
• CAFs contribute to angiogenesis, tumor metabolism, immune evasion, and premetastatic niche (PMN) formation.

Conclusions:

• CAFs are central regulators of tumor metastasis through diverse mechanisms.
• Understanding CAF functions provides a framework for developing anti-metastatic therapies.
• Targeting CAFs presents a viable strategy for improving cancer treatment outcomes.