Hsp60 expression, new locations, functions and perspectives for cancer diagnosis and therapy.
Hsp60 in eukaryotes is considered typically a mitochondrial chaperone (also called Cpn60) but in the last few years it has become clear that it also occurs in the cytosol, the cell surface, the extracellular space, and in the peripheral blood. Studies with prokaryotic models have shown that Hsp60 plays a role in assisting nascent polypeptides to reach a native conformation, and that it interacts with Hsp10 (which also resides in the mitochondria and is also named Cpn10). In addition to its role in polypeptide folding in association with Hsp10, other functions and interacting molecules have been identified for Hsp60 in the last several years. Some of these newly identified functions are associated with carcinogenesis, specifically with tumor cell survival and proliferation. Thus, assessing the levels of Hsp60 in tumor cells and in sera of cancer patients is becoming an attractive area of investigation aiming at the development of means for practical applications in clinical oncology. Since Hsp60 participates in extracellular molecular interactions and cell signalling and also in key intracellular pathways of some types of tumor cells, the idea of using Hsp60 in anti-cancer therapy (chaperonotherapy) is being investigated. The Hsp could be used either as an anticancer agent alone or in combination with tumor antigens, or as target for anti-chaperone compounds. In this article, a brief review is presented of representative research efforts aimed at assessing Hsp60 in a variety of tumors with the purpose of illustrating possible implications and applications for making early and differential diagnoses, assessing prognosis, monitoring response to treatment, and for developing novel anti-cancer strategies.
Cappello
Francesco
F
Department of Experimental Medicine, University of Palermo, Palermo, Italy. francapp@hotmail.com
Conway de Macario
Everly
E
Marasà
Lorenzo
L
Zummo
Giovanni
G
Macario
Alberto J L
AJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D018834:Chaperonin 60 / Q000378:metabolism*; D018833:Chaperonins / Q000737:chemistry; D003937:Diagnosis, Differential; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D011379:Prognosis; D017510:Protein Folding; D015398:Signal Transduction
D000970:Antineoplastic Agents; D018834:Chaperonin 60; D018833:Chaperonins