Naslov
Endoplasmic reticulum resident heat shock protein gp96 as regulator of normal and malignant growth

Autori
Radošević-Stašić, Biserka ; Jakovac, Hrvoje ; Grebić, Damir ; Mrakovčić-Šutić, Ines

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Anticancer Research. Abstracts of the eight international conference of anticancer research / Delinassios J.G. - Atena : International Institute of Anticancer Research, 2008, 3455-3456

Skup
Eight international conference of anticancer research

Mjesto i datum
Kos, Grčka, 17.10.2008. - 22.10.2008

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
endoplasmic reticulum; gp96; liver regeneration; fetoplacental unit; embriogenesis; multiple sclerosis; cervical intraepithelial neoplasia

Sažetak
Various kinds of tissue disintegration lead in the endoplasmic reticulum (ER) to activation of adaptive pathways known as the ER stress response, which is directed to correction of unfolded proteins, to the activation of proteasome-dependent ER-associated degradation of the misfolded proteins and to activation of protein translation that modulate the polypeptide traffic into the ER. A crucial role in these events plays gp96, which acts not only as a molecular chaperone, but also as an adjuvant, able to induce the specific immune response against some self and foreign antigens. Material and methods: To illustrate the mulfipotential functions of gp96 in this study we investigated its participation in conditions of: 1) normal growth (liver regeneration after partial hepatectomy, pregnancy and fetal organogenesis), 2) autoimmunity (experimental allergic encephalomyelitis) and 3) pre-malignant growth (cervical intraepithelial neoplastic lesions). Tissue expression of gp96, detected by immunohistochemistry and RT-PCR, was in animal models correlated with phenotype and cytotoxicity of hepatic and splenic mononuclear lymphatic cells against the NKT sensitive (syngeneic thymocytes) and NK-sensitive targets (YAC-1 cells), while in CIN lesions (gradus I-III) it was correlated with the intensity of neoplastic process. Results: Tissue expression of gp96 was highly upregulated in fetal and adult rapidly proliferating tissue (regenerating liver and in several fetal organs), at fetoplacental barrier, in injured tissues after autoimmune attack (on astrocytes, microglia and neurons in the brain and spinal cord during EAE), as well as in dysplastic areas of cervix (on hyperplastic epithelial cells, vascular epithelia, and glandular epithelium). Kinetic studies made in the model of liver regeneration also showed that gp96-overexpression in the liver and thymus was followed by maturation of dendritic cells, accumulation of CD3intermediate/NK1.1+/CD69+cells in the liver and CD4+CD25+Fox3+ cells in the liver and thymus, as well as by augmentation of NKT and NK-mediated cytotoxicity in the liver and in the spleen. Conclusions: The data imply that during the disturbance of morphostasis and structural integrity of the cell gp96 may protect the cells against the proteotoxic damage and serve as a natural adjuvant for chaperoning of antigenic self or oncogenic peptides into the immune surveillance pathways, contributing during the normal growth to survival of cells and reestablishment of self tolerance, and in pathological growth to both development of cancer and initiation of antitumour immune response.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA