thymosin-beta(4) and Adenocarcinoma

Thymosin β 4 (Tβ(4)) is a ubiquitous peptide that plays pivotal roles in the cytoskeletal system and in cell differentiation during embryogenesis. Recently, a role for Tβ(4) has been proposed in experimental and human carcinogenesis. This study was aimed at evaluating the correlation between Tβ(4) immunoractivity and colorectal cancer, with particular attemption to tumor cells undergoing epithelial-mesenchymal transition.. 86 intestinal biopsies were retrospectively analyzed including 76 colorectal adenocarcinomas with evident features of epithelial-mesenchymal transition, and 10 samples of normal colorectal mucosa. Paraffin sections were immunostained for Tβ(4) and for E-cadherin. Total RNA was isolated from frozen specimens obtained, at surgery, from the normal colon mucosa, the deeper regions and the superficial tumor regions in four cases of colon cancer. Tβ(4) immunoreactivity was detected in the vast majority (59/76) of colon carcinomas, showing a patchy distribution, with well differentiated areas significantly more reactive than the less differentiated tumor zones. We also noted a zonal pattern in the majority of tumors, characterized by a progressive increase in immunostaining for Tβ(4) from the superficial toward the deepest tumor regions. The strongest expression for Tβ(4) was frequently detected in invading tumor cells with features of epithelial-mesenchymal transition. The increase in reactivity for Tβ(4) matched with a progressive decrease in E-cadherin expression in invading cancer cells. At mRNA level, the differences in Tβ(4) expression between the surrounding colon mucosa and the tumors samples were not significant.. Our data show that Tβ(4) is expressed in the majority of colon cancers, with preferential immunoreactivity in deep tumor regions. The preferential expression of the peptide and the increase in intensity of the immunostaining at the invasion front suggests a possible link between the peptide and the process of epithelial mesenchymal transition, suggesting a role for Tβ(4) in colorectal cancer invasion and metastasis.

Topics: Adenocarcinoma; Cadherins; Cell Differentiation; Cell Line, Tumor; Cell Transformation, Neoplastic; Cohort Studies; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; Humans; Immunohistochemistry; Thymosin

Thymosin beta 4 (T beta 4) has been shown to be associated with tumor metastasis and angiogenesis; however, its role in pancreatic cancer has not been understood. In the current study, we examined the expression of T beta 4 in pancreatic cancer cells, and determined the effect of exogenous T beta 4 on cytokine secretion, and signal transduction in human pancreatic cancer cells.. Pancreatic cancer cell lines expressed higher amount of T beta 4 mRNA than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous T beta 4 increased the secretion of proinflammatory cytokines IL-6, IL-8 and MCP-1 in Panc-1 cells. In addition, T beta 4 activated Jun N-terminal Kinase (JNK) signaling pathways in pancreatic cancer cells.. The mRNA levels of T beta 4 were determined by real-time RT PCR. Phosphorylation of JNK in pancreatic cancer cells was determined using Bio-Plex phosphoprotein assay. The expression of cytokines in human pancreatic cancer cell lines was determined with Bio-Plex cytokine assay.. T beta 4 might be involved in stimulating human pancreatic cancer progression by promoting proinflammatory cytokine environment and activating JNK signaling pathway. Targeting T beta 4 and related molecules may be a novel therapeutic strategy for pancreatic cancer.

Topics: Adenocarcinoma; Cytokines; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Kinetics; MAP Kinase Kinase 4; Pancreatic Neoplasms; Phosphorylation; Thymosin

Zinc exhibits inhibitory effects on apoptosis, and a deficiency in this metal generally causes this type of cell death to occur. In the present study, we found that exposure to zinc results in necrosis of prostate carcinoma cells. When zinc acetate was added to LNCaP or PC-3 cells in monolayer culture, they began to detach from the culture dishes, and viability was lost after 4-8 h. Most of the cell death was found to be due to necrosis as determined by double staining with fluorescein-isothiocyanate-labeled annexin V and ethidium bromide, and by detection of hypodiploid cells. Associated with the induction of necrosis was an increase in low molecular-mass proteins, identified by HPLC analysis to be thymosin beta10, parathymosin and GAGE in LNCaP cells, and thymosin beta4, parathymosin and metallothionein in PC-3. The time course of the increase of thymosin beta10 in LNCaP cells and thymosin beta4 in PC-3 cells was consistent with that of appearance of cell detachment and dead cells. These results indicate that zinc can induce necrosis and suggest that production of proteins including beta-thymosins is involved in induction of processes leading to cell detachment.

Topics: Adenocarcinoma; Annexin A5; Apoptosis; Cell Adhesion; Cell Division; Cell Survival; Copper; DNA, Neoplasm; Humans; Male; Metallothionein; Necrosis; Neoplasm Proteins; Prostatic Neoplasms; Thymosin; Tumor Cells, Cultured; Zinc