Fibroblasts are cells of mesenchymal origin that play a crucial role in the synthesis and remodeling of the extracellular matrix (ECM), contributing to the maintenance and repair of various tissues in the body. They are typically adherent cells, anchoring themselves to the ECM and other cells through cell adhesion molecules and integrins.
However, under certain conditions, fibroblasts can become non-adherent and motile, adopting a more migratory phenotype. This transition can be induced by various factors, including changes in the ECM composition, the activation of specific signaling pathways, or the influence of cytokines and growth factors.
Some situations where non-adherent, motile fibroblasts play a role include:
- Wound healing: During the wound healing process, fibroblasts become activated and transition to a more motile phenotype, known as myofibroblasts. These cells migrate to the site of injury and contribute to tissue repair and remodeling. Myofibroblasts are characterized by the expression of alpha-smooth muscle actin (α-SMA) and enhanced contractile properties.
- Fibrosis: In fibrotic diseases, fibroblasts can become excessively activated, leading to the overproduction and deposition of ECM components, resulting in tissue scarring and organ dysfunction. Non-adherent, motile fibroblasts contribute to the progression of fibrosis by migrating to the affected areas and producing excessive ECM.
- Cancer: In the tumor microenvironment, cancer-associated fibroblasts (CAFs) are a heterogeneous population of fibroblasts that can promote tumor growth, angiogenesis, and metastasis. Some CAFs can adopt a more motile phenotype, which may contribute to the remodeling of the tumor microenvironment and facilitate cancer cell invasion and migration.
The transition of fibroblasts to a non-adherent, motile state is regulated by various signaling pathways, transcription factors, and external cues from the microenvironment. Understanding the mechanisms underlying fibroblast activation and motility is crucial for the development of potential therapeutic strategies to target fibrosis, wound healing, and cancer progression.