In Pancreatic Adenocarcinoma Alpha-Synuclein Increases and Marks Peri-Neural Infiltration

Abstract

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.

Synuclein Proteins in Cancer Development and Progression

“…An increased expression of αS in melanoma compared to normal tissue (Figure 2B) correlates perfectly with previous reports [59,69]. This is also the case for pancreatic adenocarcinoma, where an incremental expression was recently described [70]. However, there is a significant decrease in expression for this member of the family in colon adenocarcinoma in contrast with the increased protein level reported in colorectal cancer [57].…”

Novel β-synuclein Rearrangements in tumor

“…α-synuclein is not expressed in grade 1 meningioma but expressed in grade 2 and 3 meningiomas, consistent with a role of α-synuclein in disease progression [3]. In pancreatic cancer, α-synuclein expression was correlated to neurotropism, a sign of tumor progression [4]. Evidence of the β-synuclein in cancer is scarce, although its expression is seen in brain tumors including ependymoma, astrocytoma, oligodendroglioma, and medulloblastoma [5].…”

“…A diagnosis of T-ALL was made. Cytogenetic analysis of bone marrow showed a complex karyotype 45,XX,t(5;12)(q35;p13),t(7;9)(q34;q22),add(12)(p13),der(13)del(13)(q14q32)t(12;13) (p13;q34),-21[16]/46,XX [4] (Fig. 1B).…”

Exosome and lipid metabolism-related genes in pancreatic adenocarcinoma: a prognosis analysis

“…In a meta-analysis of genetic parkinsonism and cancer, SNCA was predominantly associated with gastrointestinal cancers [ 70 ], such as colorectal cancer [ 71 ]. Matteo Bianchini and co-workers discovered that α-syn was significantly upregulated in PDAC [ 72 ]. Nevertheless, our study found that SNCA was positively associated with the survival rate of PAAD patients, suggesting that an intricate molecular mechanism exists between SNCA and PAAD that needs to be further explored.…”