Naslov
Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer

Autori
Distler, U. ; Souady, J. ; Hülsewig, M. ; Drmić-Hofman, Irena ; Haier, J. ; Denz, A. ; Grützmann, R. ; Pilarsky, C. ; Senninger, N. ; Dreisewerd, K. ; Berkenkamp, S. ; Schmidt, M.A. ; Peter-Katalinić, Jasna ; Müthing, J.

Izvornik
Molecular cancer therapeutics (1535-7163) 7 (2008), 8; 2464-2475

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
CD75s; iso-CD75s-Gangliosides; pancreatic tumors; therapy

Sažetak
Pancreatic adenocarcinoma confers one of the highest mortality rates in malignant human tumors with very poor prognosis. Since as yet no treatments are available that produce a substantial survival benefit for this fatal neoplasia, new therapeutic concepts are urgently required to support cancer standard treatment. In search of tumor-associated gangliosides with therapeutic background, we probed a random collection of cancerous and adjacent normal postoperative tissue samples from 38 patients for the expression of CD75s- and iso-CD75s-gangliosides. We exhaustively analysed the expression of CD75s-1 ganglioside (IV6Neu5Ac-nLc4Cer) and structurally closely related iso-CD75s-1 ganglioside (IV3Neu5Ac-nLc4Cer) by means of immunohistochemistry of cryosections and quantitative thin-layer chromatography of tissue lipid extracts combined with mass spectrometry. CD75s-1- and iso-CD75s-1-ganglioside showed an elevated expression in 42% and 66% of the tumors, respectively, indicating a significant association with neoplastic transformation (P=0.001). Thus, increased expression of CD75s-1- and iso-CD75s-1-gangliosides renders these cell surface molecules promising candidates for oncological applications. Further statistical analysis revealed a significant enhancement of CD75s-1-ganglioside in the group of less differentiated tumors (G > 2) suggesting this ganglioside as a potential marker for poor differentiation. The CD75s-specific antitumor drug rViscumin, which represents the recombinant counterpart of the ribosome-inactivating lectin viscumin, has successfully passed clinical phase I trials and provides an opportunity for treating pancreatic cancer. Consequently, if an enhanced expression is existent in malignant tissues, we propose the targeting of CD75s-gangliosides with rViscumin as a novel potential strategy in adjuvant treatment of pancreatic malignancies.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA