Modulation of alpha 4 beta 1 and alpha 5 beta 1 integrin expression: heterogeneous effects of Q-switched ruby, Nd:YAG, and alexandrite lasers on melanoma cells in vitro.
OBJECTIVE
Integrins of the beta 1 family are cellular adhesion molecules that play an important role in cell attachment and migration by interacting with extracellular matrix molecules. Agents such as hormones, cytokines, and ultraviolet radiation have all been shown to have an integrin modulating potential. The present study indicates that radiation of Q-switched lasers is also able to induce transient changes in integrin expression levels on human melanoma cells in vitro.


METHODS
Radiation from Q-switched Ruby (694 nm), Alexandrite (755 nm), and Nd:YAG laser (1,064 nm) with fluences comparable to those that are generally used in treating dermatologic lesions were used to irradiate a subconfluent layer of human melanoma cells. After fixed time intervals, the cells were harvested either to analyse the integrin expression by flow cytometry or to investigate changes in cell attachment, spreading, and migration.


RESULTS
It was established that all three types of laser were able to cause a significant downregulation of both the alpha 4 and the common beta 1 integrin subunit. The Alexandrite and Ruby lasers also induced a decrease in alpha 5 expression; however, the cells treated with the Nd:YAG laser showed a marked upregulation of the alpha 5 subunit. The expression of the other beta 1 integrin subunits was shown to be unaltered after laser treatment. Downregulation of the alpha 4 upregulation of the alpha 5 integrin subunit expression resulted in, respectively, decreased and increased attachment and spreading on fibronectin, the extracellular matrix ligand for both the alpha 4 beta 1 and alpha 5 beta 1 integrins. Marked upregulation of the alpha 5 subunit also resulted in a higher migration rate.


CONCLUSIONS
Taken together, these results show that nonlethal doses of Q-switched laser radiation are able to induce changes in cellular behavior in vitro by modulating the integrin expression pattern.
van Leeuwen
R L
RL
Dermatology Laser Center, Harvard Medical School, Boston, Massachusetts 02114
Dekker
S K
SK
Byers
H R
HR
Vermeer
B J
BJ
Grevelink
J M
JM
D000537:Aluminum Oxide; D000538:Aluminum Silicates; D001608:Beryllium; D002448:Cell Adhesion; D002465:Cell Movement; D015536:Down-Regulation; D005353:Fibronectins / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000235:genetics*; D007834:Lasers; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D009354:Neodymium; D017469:Receptors, Fibronectin / Q000235:genetics*; D016201:Receptors, Lymphocyte Homing / Q000235:genetics*; D016029:Receptors, Very Late Antigen / Q000235:genetics*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D015019:Yttrium
D000538:Aluminum Silicates; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D009354:Neodymium; D015019:Yttrium; D000537:Aluminum Oxide; D001608:Beryllium