Expression of CD175 (Tn), CD175s (sialosyl‐Tn) and CD176 (Thomsen‐Friedenreich antigen) on malignant human hematopoietic cells

Abstract

The expression of the histo-blood group carbohydrate structures T-nouvelle (Tn, CD175), sialylated Tn (CD175s) and the Thomsen-Friedenreich disaccharide (TF, CD176) on human leukemia cell lines was analyzed by their reactivity with specific monoclonal antibodies in flow cytometry, immunohistology and immunoprecipitation. Expression of sialylated CD176 was evaluated by comparative immunostaining with anti-CD176 antibodies before and after sialidase treatment. While only few cell lines expressed unmasked CD176, sialylated CD176 was present on all hematopoietic cell lines and native lymphocytes examined. CD175 and CD175s are preferentially expressed on erythroblastic leukemia cell lines. CD175s expression in these cells is consistent with the transcription of the gene encoding the key enzyme a2,6-sialyltransferase (hST6GalNAc1). The staining intensity was reduced after methanol pretreatment of cells, indicating that these glycans are partially expressed as constituents of glycosphingolipids. Immunoprecipitation and subsequent Western blotting revealed a series of distinct high molecular glycoproteins as carriers for these carbohydrate antigens. CD34 was identified as major carrier of CD176 by immunoprecipitation and microsequencing on a KG-1 subline enriched for CD176 expression. Incubation of several CD176-positive cell lines with anti-CD176 antibodies induced apoptosis of these cells, an effect not observed with anti-CD175/ CD175s antibodies. Since the presence of naturally occurring anti-CD176 antibodies may represent a mechanism of immunosurveillance against CD176-positive tumor cells, we propose that sialylation of surface-expressed CD176-among other functionsprotects against apoptosis.

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…At 0.5 μM, the meta-substituted chlorins 514d-g still showed potent photocytotoxicity. EC 90 values varied from about 0.5 μM for 51 and 30 to less than 0.2 μM for 514f.…”

“…Lectins are not just found on the surface of cells but are easily taken up by cells as well. While tumors overexpress lectins, solid tumors have also shown an abundance of O-glycosyl moieties such as T or Tn antigens [90,91] . Very few examples of lectins covalently bound to porphyrins exist.…”

“…For the subsequent discussion an ordering by basic porphyrin type has been choosen. (49, 46, 50, 52, 42, 39, 40, 41, 43, 514a, 514b, 514f, 514g, 514d, 514e), EC 90 [151]…”

“…The difference in PDT efficacy was presumed to be due to the difference in the behavior i.e., aggregation of the glycophthalocyanines 605 and 608 in solution [359] . The tetra galactose-substituted Zn(II) phthalocyanine 602b was also tested against HT-29 human adenocarcinoma cells but provided no LD 90 values at concentrations as high as 100 µM [308] . The α-substituted zinc(II) phthalocyanines (625a/b) gave higher singlet oxygen quantum yields ranging from 0.40-0.66 compared to the metal free derivatives (624a/b, Φ Δ = 0.12-0.14) [310] .…”

CD176 antiserum treatment leads to a therapeutic response in a murine model of leukemia

“…CD176 is also expressed in leukemia and lymphoma cells (4,6), and may be a promising prognostic marker in T-cell acute lymphoblastic leukemia (7,8). In addition, CD176 is expressed in some cancer stem cells (9), and it is functionally involved in the liver metastasis process of tumors (1,10), the adhesion of human breast cancer cells to the endothelium (11,12) and the apoptosis of leukemic cells (13). Therefore, CD176 may be a promising target for cancer immunotherapy.…”