α-Synuclein is expressed in a variety of brain tumors showing neuronal differentiation

Abstract

alpha-Synuclein is presynaptic nerve terminal protein and its immunoreactivity has been observed in such neurodegenerative structures as senile plaques of Alzheimer's disease or Lewy bodies of Parkinson's disease. The physiological role of alpha-synuclein is still unknown. It is speculated that alpha-synuclein may be expressed in brain tumors, especially in those showing neuronal differentiation. We examined the immunohistochemical localization of alpha-synuclein in 77 human brain tumors. alpha-Synuclein was widely distributed in the brain tumors showing neuronal differentiation. As a result, positive immunostaining for alpha-synuclein was observed in ganglioglioma, medulloblastoma, neuroblastoma, primitive neuroectodermal tumor, pineocytoma/pineoblastoma, and central neurocytoma. Compared with other neuronal markers, the positive ratio of alpha-synuclein was not as high as synaptophysin, microtubule-associated protein 2, neuron-specific enolase and tau, but it was higher than neurofilament and chromogranin A. The expression of synaptophysin was diffusely observed in the cytoplasm, cellular processes and nucleus in tumors showing neuronal differentiation; however, the expression of alpha-synuclein was predominantly observed in the cytoplasm of the tumors as well as in the cellular processes. On the other hand, non-neuronal brain tumors such as astrocytic tumors or meningiomas were totally negative for alpha-synuclein. In conclusion, the appearance of an alpha-synuclein-positive structure was not limited to neurodegenerative diseases, but could also be detected in neoplastic cells showing neuronal differentiation.

Alpha-synuclein contributes to malignant progression of human meningioma via the Akt/mTOR pathway

“…It was reported that γ-synuclein expression is dysregulated in oral squamous cell carcinoma [14], esophageal cancer [15], and breast cancer [16]. The α-synuclein protein shows distinct tissue distributions and is predominantly expressed in brain tumors and melanomas [8, 9, 17]. In agreement with a previous study [9], we found that α-synuclein expression was very low in benign meningiomas.…”

“…There is evidence that α-synuclein differentially regulates the synthesis of melanin in melanoma and dopaminergic neuronal cells, consequently affecting cell susceptibility to ultra-violet radiation-induced injury [8]. A previous study has demonstrated that α-synuclein is expressed in a variety of brain tumors, but not in benign meningiomas [9]. However, the expression and biological relevance of α-synuclein in the malignant progression of meningiomas are not clarified.…”

Surgical management of intraventricular central neurocytoma: 92 cases

“…According to our findings (Table 7), neuron-specific enolase (NSE) was positive in 73.6% of the cases. Also, 47.1% cases showed positive for glial fibrillary acid protein (GFAP), which probably represents entrapped glial cells [9,18,46]. The results proved that CN cells have bipotential differentiation ability.…”

α-Synuclein Stimulates Differentiation of Osteosarcoma Cells

“…Although the role of syn proteins in the pathogenesis of cancer is unclear, a limited number of studies suggest that ␣-syn might be involved in the regulation of tumor differentiation. Supporting this possibility, ␣-syn was preferentially expressed in brain tumors showing neuronal differentiation (28). In cell cultures expression of ␣-syn was increased during the hematopoietic differentiation of K562 myelogenous leukemia cells (31).…”

“…Indeed, ␣-syn was widely expressed in a variety of brain tumors, such as medulloblastoma, neuroblastoma, pineoblastoma, and ganglioma (28,29). Furthermore, both ␣-and ␤-syn were shown to be expressed in the peripheral cancers, including ovarian and breast cancers (30).…”