Ceramide and sphingosine-1-phosphate act as photodynamic therapy-elicited damage-associated molecular patterns: cell surface exposure.
Molecules that appear on the surface of tumor cells after their therapy treatment may have important roles either as damage-associated molecular patterns (DAMPs) or signals for phagocytes influencing the disposal of these cells. Treatment of SCCVII and CAL27 cells, models of mouse and human squamous cell carcinoma respectively, by photodynamic therapy (PDT) resulted in the presentation of ceramide and sphingosine-1-phosphate (S1P) on the cell surface. This was documented by anti-ceramide and anti-S1P antibody staining followed by flow cytometry. The exposure of these key sphingolipid molecules on PDT-treated tumor cells was PDT dose-dependent and it varied in intensity with different photosensitizers used for PDT. The above results, together with the finding that both ceramide and S1P can activate NFκB signaling in macrophages co-incubated with PDT-treated tumor cells, establish that these two sphingolipids can act as DAMPs stimulating inflammatory/immune reactions critical for tumor therapy response.
British Columbia Cancer Agency, Vancouver, BC, Canada. Electronic address: mkorbelik@bccrc.ca.
Mladen
M
Korbelik
British Columbia Cancer Agency, Vancouver, BC, Canada.
Judit
J
Banáth
British Columbia Cancer Agency, Vancouver, BC, Canada.
Jinghai
J
Sun
Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, United States.
Daniel
D
Canals
Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, United States.
Yusuf A
YA
Hannun
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, United States.
Duska
D
Separovic
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002469:Cell Separation; D002518:Ceramides / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000628:therapy*; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D002518:Ceramides; D008246:Lysophospholipids; D051192:Receptors, Pattern Recognition; C060506:sphingosine 1-phosphate; D013110:Sphingosine
Ceramide; Damage-associated molecular patterns; Photodynamic therapy; Sphingosine-1-phosphate; Squamous cell carcinoma