title: Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer.
abstract: Pancreatic adenocarcinoma confers one of the highest mortality rates in malignant human tumors with very poor prognosis. Because 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 analyzed the expression of CD75s-1-ganglioside (IV(6)Neu5Ac-nLc4Cer) and structurally closely related iso-CD75s-1-ganglioside (IV(3)Neu5Ac-nLc4Cer) by means of immunohistology of cryosections and semiquantitative TLC 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 oncologic applications. Further statistical analysis revealed a significant enhancement of CD75s-1-ganglioside in the group of less differentiated tumors (grade >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.
authors: Institute for Medical Physics and Biophysics, University of Münster, Robert-Koch-Strasse 31, Münster, Germany.
authors: Ute
authors: U
authors: Distler
authors: Jamal
authors: J
authors: Souady
authors: Marcel
authors: M
authors: Hülsewig
authors: Irena
authors: I
authors: Drmić-Hofman
authors: Jörg
authors: J
authors: Haier
authors: Axel
authors: A
authors: Denz
authors: Robert
authors: R
authors: Grützmann
authors: Christian
authors: C
authors: Pilarsky
authors: Norbert
authors: N
authors: Senninger
authors: Klaus
authors: K
authors: Dreisewerd
authors: Stefan
authors: S
authors: Berkenkamp
authors: M Alexander
authors: MA
authors: Schmidt
authors: Jasna
authors: J
authors: Peter-Katalinic
authors: Johannes
authors: J
authors: Müthing
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000912:Antibodies, Neoplasm / Q000097:blood; D015703:Antigens, CD / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D002855:Chromatography, Thin Layer; D005732:Gangliosides / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use; D054790:Ribosome Inactivating Proteins, Type 2 / Q000627:therapeutic use*; D012799:Sialyltransferases / Q000037:antagonists & inhibitors* / Q000276:immunology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014118:Toxins, Biological / Q000627:therapeutic use*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005732:Gangliosides; D011994:Recombinant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D012799:Sialyltransferases; D014118:Toxins, Biological; C488862:mistletoe lectin I; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase