## 3 Hsp60 in Carcinogenesis
### Hsp60 in Extracellular Vesicles in Carcinogenesis  
Extracellular vesicles (EVs) are membranous particles with a diameter of 30-150 nm, which are found in blood, urine, cerebrospinal fluid, breast milk, and saliva, and are released by normal and tumor cells. The International Society for Extracellular Vesicles (ISEV) classify EVs considering their biogenesis pathways and specific markers received from the cells in which they originate, into exosomes, microvesicles, oncogenes, and apoptotic bodies; and considering size into \"small EVs\" (sEVs) and \"medium/large EVs\" (m/EVs) [124]. However, considerable morphological and biochemical heterogeneity exists among the EVs and, to complicate matters even more, many publications do not provide detailed descriptions and/or use non-standardized terminology. Because of this, we will use here EVs and exosomes as synonyms. EVs are involved in physiological and pathological processes as mediator of cell-to-cell communication by carrying proteins, \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Cancer** & **Hsp60 Level, Location and/or Status** & **Effect** & **Reference** \\ \hline Ovarian cancer & Increased Hsp60 level & Positive correlation with cancer progression and severity (poor prognosis and resistance to anti-cancer treatment) & [89; 90; 105] \\ \hline Colorectal cancer & Increased Hsp60 level & Positive correlation with cancer progression and malignancy & [93; 120] \\ \cline{2-4}  & IGFBP7-dependent down-regulation of intracellular and extracellular Hsp60 level & Involvement in tumor suppressive activity of IGFBP7 & [108] \\ \hline Prostate cancer & Increased Hsp60 level & Positive correlation with tumor progression and hormone resistance & [96] \\ \hline Gastric cancers & Increased Hsp60 level & Positive correlation with cancer progression, invasiveness, and poor overall survival. & [97; 98] \\ \hline Leukemia & Presence of Hsp60 on the cell surface & Activation/maturation of dendritic cells and generation of potent anti-tumor T-cell response & [53] \\ \cline{2-4}  & Increased Hsp60 level & Positive correlation with lower complete remission rate and shorter survival & [101] \\ \hline Glioblastoma & Increased Hsp60 level & Cytoprotective and pro-survival role & [102] \\ \cline{2-4}  & Decreased Hsp60 level & Reduced cancer cell proliferation and tumor growth & [109; 112] \\ \hline Hepatocellular carcinoma & Decreased Hsp60 level & Positive correlation with cancer progression and poor prognosis & [118] \\ \cline{2-4}  & Increased exosomal release of Hsp60 after anti-cancer treatment & Activation of anti-tumor immune response & [121] \\ \hline Pancreatic cancer & Increased Hsp60 level & Positive correlation with cancer-cell proliferation and tumor growth and progression & [111] \\ \hline Bladder carcinoma & Increased Hsp60 level & Positive correlation with resistance to anti-cancer treatment & [105] \\ \cline{2-4}  & Decreased Hsp60 level & Positive correlation with higher tumor stage and cancer recurrence & [122] \\ \hline Renal cell carcinoma & Decreased Hsp60 & Disruption of mitochondria homeostasis and positive correlation with cancer progression & [117] \\ \hline Large bowel cancer & Increased intracellular and exosomal Hsp60 level & Positive correlation with tumor development and progression & [123] \\ \hline Thyroid cancers & Increased intracellular and exosomal Hsp60 level & Positive correlation with tumor progression & [99; 100] \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Cont. lipids, and nucleic acids (DNA, mRNA, and miRNAs), that affect recipient cells and modify their functions [125; 126; 127; 128; 129; 130; 131]. Their content may vary depending on the cell type that produces them, but in general EVs carry a range of diverse proteins, such as tumor susceptibility gene 101 (TSG101); integrins; and tetraspanins such as CD9, CD53, CD63, CD81, and CD82 [132; 133]. EVs are thought to play a role in the remodelling of the pericellular microenvironment that is crucial in maintaining tumor growth and recurrence [123; 134].