Patterns of GRP78 and MTJ1 expression in primary cutaneous malignant melanoma

Abstract

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.

Glucose-regulated protein 78 and heparanase expression in oral squamous cell carcinoma: correlations and prognostic significance

“…The findings of the present study on excised OSCC were consistent with those of previous reports, and suggest that increased expression of GRP78 may be a feature of many malignant tumors found in humans. Some papers have shown that the regulation and expression of GRP78 are associated with shorter overall survival [20-22]. The present study demonstrated that positive GRP78 expression could also act as a predictor of shorter overall survival.…”

Roles of GRP78 in physiology and cancer

“…The exact mechanism still needs to be uncovered. So far, cell surface GRP78 has been identified in human prostate cancer [Gonzalez-Gronow et al , 2006], ovarian cancer [Chinni et al, 1997], gastric cancer [Rauschert et al, 2008], and melanoma [Papalas et al, 2010]. On infection diseases, GRP78 is identified as a coreceptor of MHC-I molecule for coxsackievirus internalization [Triantafilou et al, 2002] and thus enhances the magnitude of virus infection.…”

Antitumor agent 25-epi Ritterostatin GN1N induces endoplasmic reticulum stress and autophagy mediated cell death in melanoma cells

“…Glucose-regulated protein 78 (GRP78) is thought to be a major sensor of ER stress and is associated with melanoma progression and increased drug resistance in melanoma and other cancers (18,52–54). Since our findings indicated that autophagy was activated by 25- epi Ritterostatin G N 1 N in melanoma cells, we investigated the effect of 25- epi Ritterostatin G N 1 N on GRP78 expression.…”