Lectin-Defined Cell Surface Glycoconjugates of Pancreatic Cancer Cells and Their Nonmalignant Counterparts

In this study we investigated the functional role of FAP-1 as a potential inhibitor of CD95 (Fas, APO-1)-mediated apoptosis in pancreatic cancer cells. Stable transfection of the CD95-sensitive, FAP-1-negative cell line Capan-1 with an FAP-1 cDNA resulted in a strongly decreased sensitivity to CD95-induced apoptosis, as measured by DNA fragmentation and caspase-3 activity. Inhibition of cellular protein tyrosine phosphatases with orthovanadate dose-dependently increased CD95-induced apoptosis in CD95-resistant FAP-1-positive Panc89 and Capan-1-FAP-1 cells almost to the level seen in wild-type Capan-1 cells. Blocking the CD95/FAP-1 interaction in Panc89 cells by cytoplasmic microinjection of a synthetic tripeptide mimicking the C terminus of CD95 resulted in a mean 5.5-fold increase in apoptosis compared to cells that received a control peptide. Using confocal laser scanning microscopy we show that in Panc89 cells FAP-1 is mainly associated with the Golgi complex and with peripheral vesicles. FAP-1 displayed enhanced colocalization with CD95 upon CD95 stimulation in the Golgi complex but not in surface-associated vesicles. This correlated with a decrease in plasma membrane staining for CD95 as determined by FACS analysis. Inhibition of Golgi anterograde transport by brefeldin A abolished the anti-CD95-induced colocalization of FAP-1 and CD95 as well as the decrease in cell-surface-associated CD95. Finally, we demonstrate by immunohistochemistry that FAP-1 is strongly expressed in tumor cells from pancreatic carcinoma tissues. Taken together, these results show that FAP-1 can protect pancreatic carcinoma cells from CD95-mediated apoptosis, probably by preventing anti-CD95-induced translocation of CD95 from intracellular stores to the cell surface.

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The roles of cell surface attachment molecules and coagulation Factor X in adenovirus 5-mediated gene transfer in pancreatic cancer cells

Cancer Gene Therapy ◽

10.1038/cgt.2011.17 ◽

2011 ◽

Vol 18 (7) ◽

pp. 478-488 ◽

Cited By ~ 2

Author(s):

S Hamdan ◽

C S Verbeke ◽

N Fox ◽

J Booth ◽

G Bottley ◽

...

Keyword(s):

Pancreatic Cancer ◽

Gene Transfer ◽

Cell Surface ◽

Cancer Cells ◽

Coagulation Factor ◽

Factor X ◽

Surface Attachment ◽

Pancreatic Cancer Cells ◽

Adenovirus 5

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Abstract 3828: Pritumumab mAb binds cell surface expressed vimentin on pancreatic cancer cells and inhibits tumor growth

10.1158/1538-7445.am2018-3828 ◽

2018 ◽

Author(s):

Ivan Babic ◽

Natsuko Nomura ◽

Eric Glassy ◽

Elmar Nurmemmedov ◽

Venkata Yenugonda ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Surface ◽

Tumor Growth ◽

Cancer Cells ◽

Pancreatic Cancer Cells

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Novel Pancreatic Cancer Therapy Targeting Cell Surface Glycans by Liposomes Modified with rBC2LCN Lectin

European Surgical Research ◽

10.1159/000513430 ◽

2020 ◽

Vol 61 (4-5) ◽

pp. 113-122

Author(s):

Sota Kimura ◽

Tatsuya Oda ◽

Osamu Shimomura ◽

Tsuyoshi Enomoto ◽

Shinji Hashimoto ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Therapy ◽

Cell Surface ◽

Cancer Cells ◽

Cancer Cell ◽

Human Pancreatic Cancer ◽

Pancreatic Cancer Cells ◽

Cell Surface Glycans

Introduction: Since the outermost layer of cancer cells is covered with various glycans, targeting these groups may serve as an effective strategy in cancer therapy. We previously reported that fucosylated glycans are specifically expressed on pancreatic cancer cells, and that a protein specifically binding to these glycans, namely rBC2LCN lectin, is a potential guiding drug carrier. In the present study, a novel type of glycan-targeting nanoparticle was developed by modifying the surface of doxorubicin-containing liposomes with rBC2LCN lectin. The efficiency and specificity of this formulation, termed Lec-Doxosome, were examined in vitro and in vivo in human pancreatic cancer models. Methods: Lec-Doxosome was prepared by a post-insertion method based on the insertion of rBC2LCN lectin into the liposomal surface via a lipid linker. The in vitro cellular binding, uptake, and cytotoxicity of Lec-Doxosome were compared with the corresponding parameters in the unmodified liposomes by applying to human pancreatic cancer cell line (Capan-1) with affinity for rBC2LCN lectin. For the in vivo assay, Lec-Doxosome was intravenously injected once per week for a total of 3 weeks into mice bearing subcutaneous tumors. Results: The in vitro application of Lec-Doxosome resulted in a 1.2- to 1.6-fold higher intracellular doxorubicin accumulation and a 1.5-fold stronger cytotoxicity compared with the respective rates of accumulation and cytotoxicity in the unmodified liposomes. In vivo, Lec-Doxosome reduced the mean tumor weight (368 mg) compared with that in mice treated with unmodified liposomes (456 mg), without causing any additional adverse events. Conclusion: It was demonstrated from the results obtained herein that rBC2LCN lectin is a potent modifier, as a means for boosting the efficiency of nanoparticles in the targeting of cancer cell surface glycans.

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