Regulation of the New Coexpressed CD55 (Decay-Accelerating Factor) Receptor on Stomach Carcinoma Cells Involved in Antibody SC-1–Induced Apoptosis

Hensel, Frank; Hermann, R. Schulte; Brändlein, Stephanie; Krenn, Veit; Schmausser, B; Geis, Steffen; Müller‐Hermelink, Hans Konrad; Vollmers, H. Peter

doi:10.1038/labinvest.3780369

Cited by 42 publications

(28 citation statements)

References 39 publications

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“…22,23 For example, the human antibody SC-1 detects a new isoform of the complement protection molecule CD55 on stomach cancer cells, 51,52 and the human antibody PAM-1 binds to a new variant of the growth factor receptor, CFR-1. 26,53 Recently, a variant of GRP94, modified in its carbohydrate structure, was detected in more aggressive cancer prostate tissues but not normal tissues.…”

Section: Discussionmentioning

confidence: 99%

A new tumor-specific variant of GRP78 as target for antibody-based therapy

Rauschert

Brändlein

Holzinger

et al. 2008

Laboratory Investigation

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121

104

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The chaperone GRP78 is a member of the heat-shock protein 70 (HSP70) family and is responsible for cellular homeostasis by preventing stress-induced apoptosis. GRP78 is expressed in all cells of the body. In malignant cells, which are permanently exposed to environmental stress, GRP78 is overexpressed and increased levels can be found in the cytoplasm and on the cell membrane. Thus, GRP78 promotes tumor proliferation, survival, metastases and resistance to a wide variety of therapies. Like other tumor-specific membrane molecules, GRP78 can also be present on cancer cells in a variant form. This modification qualifies it as a target for immune surveillance and antibody responses. The fully human monoclonal IgM antibody, SAM-6, was isolated from a gastric cancer patient and it binds to a new variant of GRP78 with a molecular weight of 82 kDa. The epitope is an O-linked carbohydrate moiety and is specific for malignant cells. These data show that cancer-specific modifications of cell-surface protection molecules are (a) subject of an immune response and (b) ideal targets for new therapeutical approaches.

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Section: Discussionmentioning

confidence: 99%

A new tumor-specific variant of GRP78 as target for antibody-based therapy

Rauschert

Brändlein

Holzinger

et al. 2008

Laboratory Investigation

Self Cite

121

104

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“…Isolation of membrane proteins from tumor cells was performed as described previously (16). Reducing SDS-PAGE gels (10%) and Western blotting of membrane proteins were performed using standard protocols.…”

Section: Methodsmentioning

confidence: 99%

“…The antibody SC-1 binds to a modified isoform of decay acceleration factor-B, specifically expressed on the membrane of stomach carcinoma cells (8,14,16), and induces apoptosis by cross-linking of the receptor (14, 16, 18 -23) both in vitro and in experimental in vivo systems (8,18,19). Clinical studies of SC-1 showed that regression and apoptosis of primary stomach cancers can be induced without any detected toxic cross-reactivity to normal tissue (22).…”

Section: Introductionmentioning

confidence: 99%

Lipoptosis

et al. 2004

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A balanced lipid metabolism is crucial for all cells. Disturbance of this homeostasis by nonphysiological intracellular accumulation of fatty acids can result in apoptosis. This was proven in animal studies and was correlated to some human diseases, like lipotoxic cardiomyopathy. Some metabolic mechanisms of lipo-apoptosis were described, and some causes were discussed, but reagents, which directly induce lipo-apoptosis, have thus far not been identified. The human monoclonal IgM antibody SAM-6 was isolated from a stomach cancer patient by using the conventional human hybridoma technology (trioma technique). The addition of SAM-6 to tumor cells leads to an increase in the intracellular accumulation of neutral lipids, followed by tumor cell apoptosis. The antibody SAM-6 does not react with noncancerous human epithelial and fibroblastic cells, because the M r 140,000 membrane molecule, recognized by the antibody, is specifically expressed on human malignant cells. The antibody is coded by the germ-line genes IgHV3-30.3*01 and IgLV3-1*01 and is a component of the innate immunity to cancer. In this article, we describe an antibodyinduced tumor-specific cell death, named lipoptosis. This is, to our knowledge, the first description of this specific form of lipo-apoptosis as an antibody-mediated mechanism of tumor cell killing.

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“…Specifically, SC-1 was shown to react with a 50-kDa surface molecule expressed by gastric carcinoma cells; it induces apoptosis and inhibits proliferation of gastric carcinoma cells in vitro and can significantly reduce gastric cancer growth in vivo [236]. Also, CH401 was reported to be able to kill gastric cancer cells overexpressing the erbB2 protein in vitro by inducing apoptosis in the cells [237]. In addition, E-cadherin mutation-specific monoclonal antibodies were reported to react with 13% of Ecadherin-positive diffuse-type gastric cancers [238].…”

Section: Therapeutic Applicationsmentioning

confidence: 99%