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Fibroblast migration on fibronectin requires three distinct functional domains
Richard A F Clark1, Jian-Qiang An, Doris Greiling
1Department of Dermatology, School of Medicine, SUNY at Stony Brook, Stony Brook, New York 11794-8165, USA. Richard.Clark@sunysb.edu
The Journal of Investigative Dermatology
|November 25, 2003
Summary
Fibronectin enables stromal cell migration, but requires specific domains and multiple receptors for human fibroblast movement. This complex regulation likely constrains normal cell mobility, with dysregulation potentially linked to cancer cell invasion.
Area of Science:
- Cell Biology
- Biochemistry
- Extracellular Matrix Research
Background:
- Mesenchymal cell migration is crucial for development and healing but is normally restricted.
- Fibronectin (FN) acts as a substrate for cell migration through interactions with integrin and nonintegrin receptors.
- Understanding the specific FN domains and receptor cooperation is key to deciphering cell motility regulation.
Purpose of the Study:
- To identify the functional domains of fibronectin essential for human fibroblast migration.
- To investigate the role of specific cell attachment sequences and receptor types in mediating this migration.
- To elucidate the regulatory mechanisms controlling mesenchymal cell movement on fibronectin.
Main Methods:
- Utilized synthetic peptides and recombinant proteins to map functional domains on fibronectin.
- Assessed human fibroblast attachment and migration on various fibronectin fragments.
- Investigated the necessity of specific cell adhesion sequences (RGD, PHSRN) and regions (heparin, IIICS).
Main Results:
- Fibronectin type III repeats 9 and 10, containing RGD and PHSRN sequences, supported high fibroblast attachment but not migration.
- Specific sequences within the fibronectin heparin domain and IIICS region were found to be essential for fibroblast migration.
- Cooperation between multiple integrin and nonintegrin receptors is necessary for effective fibroblast migration on fibronectin.
Conclusions:
- Fibronectin-mediated fibroblast migration is a complex process requiring specific domains and synergistic receptor interactions.
- The stringent requirements for migration suggest a mechanism for constraining normal mesenchymal cell mobility.
- Dysregulation of these migration constraints may play a role in pathological conditions like cancer cell invasion.