Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response

• Published in: International journal of oncology Vol. 38; no. 2; pp. 521 - 527
• Main Authors: SEPAROVIC, D, BIELAWSKI, J, PIERCE, J. S, MERCHANT, S, TARCA, A. L, BHATTI, G, OGRETMEN, B, KORBELIK, M
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.02.2011
• Subjects: Animals; Biological and medical sciences; Biomarkers - metabolism; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Ceramides - pharmacology; Dermatology; Disease Models, Animal; Female; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Medical sciences; Mesoporphyrins - therapeutic use; Mice; Mice, Inbred C3H; Photochemotherapy; Photosensitizing Agents - therapeutic use; Pyridinium Compounds - pharmacology; Spectrometry, Mass, Electrospray Ionization; Sphingolipids - metabolism; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Phosphates; Skin disease; Basal cell carcinoma; sphingolipids; dihydrosphingosine-1-phosphate; Biological marker; Cancerology; Established cell line; Sphingosine-1-phosphate; Ceramide; Squamous cell carcinoma; Photodynamic therapy; Foscan; Cure; C6-pyridinium ceramide; Treatment efficiency; Rodentia; Sphingolipid; dihydroceramide; Malignant tumor; dihydrosphingosine; Vertebrata; Mammalia; Mouse; Analog; Animal; Combined treatment; Cancer
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2010.863

To improve anticancer therapeutic success of photodynamic therapy (PDT), combination treatments represent a viable strategy. Sphingolipid analogs combined with anticancer drugs can enhance tumor response. We have shown that LCL29, a C6-pyridinium ceramide, promotes therapeutic efficacy of Photofrin-PDT in mouse SCCVII squamous cell carcinoma tumors. The long-term effect of the combination PDT + LCL29 is unknown. In this study we used the same model to test the long-term curative potential of Foscan-PDT + LCL29. We show that treatment of SCCVII tumors with the combination led to enhanced long-term tumor cure compared to PDT alone. LCL29 itself did not prevent tumor growth. All treatments triggered early increases in tumor-associated C16-ceramide, C18-ceramide, dihydrosphingosine, and global levels of dihydroceramides. PDT-evoked increases in tumor-associated sphingosine-1-phosphate and dihydrosphingosine-1-phosphate remained elevated or were attenuated after the combination, respectively; in contrast, LCL29 had no effect on these two sphingolipids. Our data demonstrate that adjuvant LCL29 improves PDT long-term therapeutic efficacy, implying translational potential of the combination. Furthermore, our findings indicate that changes in the sphingolipid profile might serve as predictive biomarkers of tumor response to treatments.