Glucose-regulated protein of 78？kD (GRP78) is a chaperone protein mainly located in the endoplasmic reticulum (ER). This protein is normally present at low levels in adult cells but its expression is triggered by ER stress including glucose deprivation and hypoxia. In tumor cells, it is overexpressed with fraction of protein found at the cell surface. This paper presents the physiology of GRP78 in the context of ovarian cancer and its potential use as drug delivery systems targeting ovarian cancer cell. 1. Introduction Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) chaperone protein belonging to the heat shock protein 70 family. It consists of two functional domains, a 44？kDa N-terminal ATPase and a 20？kDa C-terminal polypeptide-binding domain, and a variable 10？kDa C-terminal tail of unknown function. This protein, as other members of this family, plays an essential role in protein biosynthesis (for review, see [1]). It facilitates folding and assembly of newly synthesized proteins and prevents intra- or intermolecular aggregation during stress conditions [2, 3]. GRP78 expression is induced by a variety of environmental and physiological stress conditions leading to impairment of essential ER functions and homeostasis in order to protect organs and tissues against apoptosis [4]. Its expression also varies with developmental stages and tissue specificity. A low basal level is identified in most adult tissues whereas it is highly induced in cancer [5, 6]. GRP78 expression is induced under such conditions as hypoxia and nutrient deprivation, partially explaining its high level in tumour cells [7]. GRP78 generally resides inside the ER lumen. However, GRP78 is also found at the cell surface in a wide variety of cancer cells, including neuroblastoma, lung adenocarcinoma, colon adenocarcinoma, ovarian tumour cells [8], prostate cancer [9], proliferating endothelial cells, and, more generally, stressed tumour cells [10]. It is still unknown how GRP78 localizes to the various cellular compartments, and its physiological role at the cell surface membrane is still not fully understood. A hypothesis is that upon GRP78 overexpression, it escapes to ER retention and reaches cell surface. Some proteins are involved in GRP78 relocation, as MTJ-1 and Par-4 [11, 12]. Through its binding to other proteins at the cell surface, GRP78 mediates cell-signalling pathways. For example, cell surface GRP78 acts as a receptor for alpha-2-macroglobulin, leading to activation of PAK-2, to induction of cell motility [12, 13], and to activation of MAPK and PI3K
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