alpha-synuclein and Adenocarcinoma

α-Synuclein (α-syn) is a protein involved in neuronal degeneration. However, the family of synucleins has recently been demonstrated to be involved in the mechanisms of oncogenesis by selectively accelerating cellular processes leading to cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers, with a specifically high neurotropism. The molecular bases of this biological behavior are currently poorly understood. Here, α-synuclein was analyzed concerning the protein expression in PDAC and the potential association with PDAC neurotropism. Tumor (PDAC) and extra-tumor (extra-PDAC) samples from 20 patients affected by PDAC following pancreatic resections were collected at the General Surgery Unit, University of Pisa. All patients were affected by moderately or poorly differentiated PDAC. The amount of α-syn was compared between tumor and extra-tumor specimen (sampled from non-affected neighboring pancreatic areas) by using in situ immuno-staining with peroxidase anti-α-syn immunohistochemistry, α-syn detection by using Western blotting, and electron microscopy by using α-syn-conjugated immuno-gold particles. All the methods consistently indicate that each PDAC sample possesses a higher amount of α-syn compared with extra-PDAC tissue. Moreover, the expression of α-syn was much higher in those PDAC samples from tumors with perineural infiltration compared with tumors without perineural infiltration.

Topics: Adenocarcinoma; alpha-Synuclein; Carcinoma, Pancreatic Ductal; Humans; Pancreatic Neoplasms

The synucleins (alpha, beta, and gamma) are a family of small cytoplasmic proteins that are expressed predominantly in neurons. alpha synuclein has attracted considerable attention due to its involvement in neurodegenerative diseases. Abnormal expression of gamma synuclein has recently been reported in some breast tumors. In this study, the authors examined a panel of breast and ovarian carcinomas for expression of alpha, beta, and gamma synucleins.. Normal breast and ovary tissue samples, tissue from ovaries of women at high risk of ovarian carcinoma, and tissue from breast and ovarian carcinomas were screened by immunohistochemistry and Western blot analysis for synuclein expression.. Synucleins were not detectable by Western blot analysis in normal breast tissue. Eighty-two percent (14 of 17) of Stage III/IV breast ductal carcinomas expressed beta synuclein, gamma synuclein, or both simultaneously. Expression of alpha synuclein was not detected in breast carcinomas by Western blot analysis. Synuclein (alpha, beta, and gamma) expression was not detectable by immunohistochemistry in normal ovarian epithelium. Eighty-seven percent (39 of 45) of ovarian carcinomas were found to express at least 1 type of synuclein, and 42% (19 of 45) expressed all 3 synucleins (alpha, beta, and gamma) simultaneously. Highly punctate gamma synuclein expression was also observed in 20% of preneoplastic lesions of the ovary, including epithelial inclusion cysts, hyperplastic epithelium, and papillary structures, suggesting that gamma synuclein up-regulation may occur early in the development of some ovarian tumors.. alpha, beta, and gamma synuclein are expressed in a high percentage of ovarian and breast carcinomas, and abnormal gamma synuclein expression may occur early in the development of ovarian carcinoma.

Topics: Adenocarcinoma; alpha-Synuclein; beta-Synuclein; Blotting, Western; Breast; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Cystadenocarcinoma, Papillary; Epithelial Cells; Female; gamma-Synuclein; Gene Expression Regulation, Neoplastic; Humans; Hyperplasia; Immunohistochemistry; Nerve Tissue Proteins; Ovarian Cysts; Ovarian Neoplasms; Ovary; Phosphoproteins; Polymerase Chain Reaction; Precancerous Conditions; Synucleins; Tumor Cells, Cultured