Glucose regulated proteins in cancer progression, Drug resistance and immunotherapy

Fu, Yong; Lee, Amy

doi:10.4161/cbt.5.7.2970

Cited by 212 publications

(190 citation statements)

References 48 publications

(63 reference statements)

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“…GRP78 SAM-6 is coexpressed with wild-type GRP78, which has a molecular weight of 78 kDa, and was recently found on the surface of certain cell types. 19,20,[27][28][29][30][31] The SAM-6-specific variant of GRP78 is post-transcriptionally modified and the epitope is a carbohydrate structure, which is specific for the plasma membrane molecule, but is not present on the intracellular GRP78 molecules.…”

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

119

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

119

104

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“…45 Of the GRP family, GRP78 is the best studied. Robust induction of GRP78 occurs in many malignancies.…”

Section: Discussionmentioning

confidence: 99%

Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma

et al. 2010

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Cell surface expression of glucose-regulated protein 78 (GRP78) occurs in several types of cancer; however, its role in the behavior of primary cutaneous melanoma is not well studied. The association of cell surface GRP78 with other proteins such as MTJ1 stimulates cell proliferation. In this study, we characterized the pattern of expression of GRP78 and MTJ1 in invasive primary cutaneous melanomas and analyzed the relationships between the pattern of expression and various clinicopathological parameters. We found two patterns of GRP78 expression in invasive primary cutaneous melanoma. One pattern showed a gradual fading of protein expression from superficial to deeper levels within the same tumor. The second pattern of expression showed a similar fading with an abrupt regaining of expression at the deep invasive edge of the melanoma. These two distinct patterns of GRP78 expression correlated with both patient survival and depth of tumor invasion. A moderate MTJ1 expression was found to be associated with decreased patient survival; however, no significant associations were observed between patterns of GRP78 and MTJ1 expression. Our study (1) describes two distinct patterns of GRP78 in invasive primary cutaneous melanoma, (2) inversely correlates regain of GRP78 expression with patient survival, and (3) suggests a modifying effect of MTJ1 on GRP78 in enhancing tumor aggressiveness.

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“…It remains to be determined whether the off-site expression of molecular chaperones is restricted to specific types of cancer and what fractions of these chaperones are presented on different cellular locations in tumor cells. Nonetheless, in certain cancers, the surface-localized GRP78 has been utilized as a beacon to deliver therapeutic agents specifically into cancer cells (Fu and Lee, 2006). Biologic factors that predict a favorable outcome for neuroblastoma patients are usually associated with differentiation or regression of neuroblastoma cells and early clinical stages.…”

Section: Resultsmentioning

confidence: 99%