Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer
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Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer. / Distler, Ute; Souady, Jamal; Hülsewig, Marcel; Drmić-Hofman, Irena; Haier, Jörg; Denz, Axel; Grützmann, Robert; Pilarsky, Christian; Senninger, Norbert; Dreisewerd, Klaus; Berkenkamp, Stefan; Schmidt, M Alexander; Peter-Katalinic, Jasna; Müthing, Johannes.
In: MOL CANCER THER, Vol. 7, No. 8, 08.2008, p. 2464-75.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer
AU - Distler, Ute
AU - Souady, Jamal
AU - Hülsewig, Marcel
AU - Drmić-Hofman, Irena
AU - Haier, Jörg
AU - Denz, Axel
AU - Grützmann, Robert
AU - Pilarsky, Christian
AU - Senninger, Norbert
AU - Dreisewerd, Klaus
AU - Berkenkamp, Stefan
AU - Schmidt, M Alexander
AU - Peter-Katalinic, Jasna
AU - Müthing, Johannes
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - Adenocarcinoma
KW - Antibodies, Neoplasm
KW - Antigens, CD
KW - Antineoplastic Agents
KW - Biomarkers, Tumor
KW - Chemotherapy, Adjuvant
KW - Chromatography, Thin Layer
KW - Gangliosides
KW - Humans
KW - Immunohistochemistry
KW - Microscopy, Fluorescence
KW - Pancreatic Neoplasms
KW - Recombinant Proteins
KW - Ribosome Inactivating Proteins, Type 2
KW - Sialyltransferases
KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
KW - Toxins, Biological
U2 - 10.1158/1535-7163.MCT-08-0353
DO - 10.1158/1535-7163.MCT-08-0353
M3 - SCORING: Journal article
C2 - 18723492
VL - 7
SP - 2464
EP - 2475
JO - MOL CANCER THER
JF - MOL CANCER THER
SN - 1535-7163
IS - 8
ER -
