Glycosphingolipids of normal and leukemic human leukocytes

Ba, Macher; Lee, WM; Ma, Westrick

doi:10.1007/bf00234409

Cited by 17 publications

(18 citation statements)

References 39 publications

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“…Thus, the overall fluorescence intensity of CD75s-positive tumor areas exceeded by far that of leukocytes (most likely polymorphonuclear leukocytes; that is, neutrophilic granulocytes; ref. 28). In all cases, sections incubated with mouse IgG1 isotype control, chicken preimmune serum as well as the secondary dichlorotriazinylamino fluorescein -labeled antibodies only, did not stain.…”

Section: Immunohistochemical Detectionof Tumor-associated Cd75s-ganglmentioning

confidence: 86%

“…Tumor-infiltrating macrophages (33) and granulocytes (28) can significantly contribute to the total cell population of certain tumors and thus to the composition of GSL extracts obtained from solid tumors. The fact that granulocytes and, to a minor extent, macrophages do express type II gangliosides (22,34) indicates the necessity of a thorough microscopic evaluation of the tumor tissue for the presence of neutrophils and macrophages.…”

Section: Discussionmentioning

confidence: 99%

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

Distler

Souady²,

Hülsewig³

et al. 2008

Molecular Cancer Therapeutics

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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 tumorassociated 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. [Mol Cancer Ther 2008;7(8):2464 -75]

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Section: Immunohistochemical Detectionof Tumor-associated Cd75s-ganglmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

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

Distler

Souady²,

Hülsewig³

et al. 2008

Molecular Cancer Therapeutics

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“…Previously, Macher et al 31 reported Gb 4 in 6 of 6 clinical ANLLs, with Gb 4 accounting for 20% to 75% of the total GSL4 present. Gb 3 and/or Gb 4 was also identified in KG1, THP-1, and K526 cells, 3 human ANLL cell lines.…”

Section: Discussionmentioning

confidence: 95%

“…Similar findings have been reported by others and suggest a dramatic increase in total neutral GSL content with neutrophilic maturation. 30,31,81 Neutrophilic maturation also appears to be associated with a relative and absolute increase in LacCer content, as evidenced by the percent LacCer and LacCer/ GlcCer ratio. Biologically, high LacCer expression on mature neutrophils may play a role in inflammation and infection.…”

Section: Discussionmentioning

confidence: 99%

“…26 Gb 3 and/or Gb 4 has also been identified in 3 immortalized human myeloid leukemia cell lines, KG1, K526, and THP-1, as well as a small number of clinical acute nonlymphocytic leukemia (ANLL) samples. [27][28][29][30][31][32] In addition, there is evidence that parvovirus B19, which recognizes Gb 4 , can infect early myeloid cells, decrease myeloid progenitors, and inhibit granulocyte-monocyte colony (CFU-GM) formation in vivo. 18,[33][34][35][36] In contrast, globo GSLs are not expressed by either mature neutrophils or chronic myeloid leukemia (CML) cells.…”

Section: Introductionmentioning

confidence: 99%

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Glycosphingolipid expression in acute nonlymphocytic leukemia: common expression of shiga toxin and parvovirus B19 receptors on early myeloblasts

Cooling

Zhang

Naides

et al. 2003

Blood

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Glycosphingolipids (GSLs) are complex macromolecules on cell membranes that have been shown to play a role in neutrophil differentiation, activation, phagocytosis, and adhesion to both microorganisms and vascular endothelium. Because GSLs are often cryptic antigens on cell membranes, little is known regarding GSL expression in early myelopoiesis. To study the latter, myeloblasts were collected from patients with acute nonlymphocytic leukemia (ANLL) who required therapeutic leukocytopheresis for hyperleukocytosis. The neutral GSLs were isolated and identified by high-performance thin-layer chromatography (HPTLC), HPTLC immunostaining, gas chromatography, nuclear magnetic resonance, and fast atom bombardment-mass spectrometry. Like mature peripheral blood neutrophils, myeloblasts expressed glucosylceramide, lactosylceramide, and the neolacto-family GSLs, lactotriaosylceramide and neolactotetraosylceramide. Unlike neutrophils and chronic myeloid leukemia, most ANLL samples also expressed the globo-series GSLs, globotriaosylceramide and globotetraosylceramide. Globo GSL expression was strongly associated with a myeloblastic (ANLL M0-M2) and monoblastic phenotype (M5). A weak association was also noted with expression of either lymphoid (P < .

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Plasma membrane lipid composition of vinblastine sensitive and resistant human leukaemic lymphoblasts

May

Wright

Dyne

et al. 1988

Intl Journal of Cancer

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Plasma membranes purified 32- to 45-fold were isolated from leukaemic T-lymphoblasts, both sensitive and resistant to the Vinca alkaloid vinblastine. On development of drug resistance there was a very significant elevation of ether lipid content. 1-0-alkyl phospholipid increased by 200% with a smaller 30% increase in 1-0-alkenyl phospholipid. Cholesterol and phospholipid levels were also found to increase by 50% and 30% respectively, while the lipid to protein ratio increased by 60%. More modest changes were observed in the fatty acid composition of the membranes, with an alteration in the double bond index from 35.3 to 41.2. These lipid changes may have important implications in the changes to membrane permeability that develop with drug resistance.

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Glycosphingolipids of normal and leukemic human leukocytes

Cited by 17 publications

References 39 publications

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

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

Glycosphingolipid expression in acute nonlymphocytic leukemia: common expression of shiga toxin and parvovirus B19 receptors on early myeloblasts

Plasma membrane lipid composition of vinblastine sensitive and resistant human leukaemic lymphoblasts

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