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Parkinson's disease-related protein, alpha-synuclein, in malignant melanoma.

Matsuo Y, Kamitani T - PLoS ONE (2010)

Bottom Line: However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi.Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Center for Molecular Chaperone/Radiobiology and Cancer Virology, Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.

ABSTRACT

Background: Melanoma is the major cause of skin cancer death worldwide. Parkinson's disease is a neurodegenerative disorder that is caused by mutation of alpha-synuclein or other genes. Importantly, epidemiological studies have reported co-occurrence of melanoma and Parkinson's disease, suggesting that these two diseases could share common genetic components.

Methodology/principal findings: Recently, we found that human melanoma cell lines highly express alpha-synuclein, whereas the protein is undetectable in the non-melanoma cancer cell lines tested. To investigate the expression of alpha-synuclein in human melanoma tissues, we immunostained sections of melanoma, nevus, non-melanocytic cutaneous carcinoma, and normal skin. alpha-Synuclein was positively detected in 86% of the primary and 85% of the metastatic melanoma sections, as well as in 89% of nevus sections. However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.

Conclusions/significance: The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi. Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

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Related in: MedlinePlus

Expression levels of α-synuclein in human melanoma cell lines.Expression of endogenous α-synuclein was examined in melanoma cell lines by Western blotting using mouse monoclonal anti-α-synuclein antibody 4D6. Total cell lysates of HeLa cells expressing FLAG-tagged α-synuclein and SK-MEL28 cells were loaded as positive controls. To demonstrate expression of melanoma markers, we performed Western blotting using monoclonal antibodies against MART-1 and HMB-45. To demonstrate equal loading amounts of total cell lysates, Western blotting using anti-actin antibody was also performed (bottom panel). The detected proteins are indicated on the right. Molecular size markers are shown in kilodaltons.
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pone-0010481-g003: Expression levels of α-synuclein in human melanoma cell lines.Expression of endogenous α-synuclein was examined in melanoma cell lines by Western blotting using mouse monoclonal anti-α-synuclein antibody 4D6. Total cell lysates of HeLa cells expressing FLAG-tagged α-synuclein and SK-MEL28 cells were loaded as positive controls. To demonstrate expression of melanoma markers, we performed Western blotting using monoclonal antibodies against MART-1 and HMB-45. To demonstrate equal loading amounts of total cell lysates, Western blotting using anti-actin antibody was also performed (bottom panel). The detected proteins are indicated on the right. Molecular size markers are shown in kilodaltons.

Mentions: α-Synuclein protein is highly expressed in the human malignant melanoma SK-MEL28 cell line, suggesting that it may be expressed in other melanoma cell lines. To test this possibility, we examined the expression levels of α-synuclein and two melanoma markers (MART-1 and HMB-45) in 3 other malignant melanoma cell lines, A-375, MeWo, and WM266-4, by Western blotting. HeLa cell transfectants expressing FLAG-tagged α-synuclein and SK-MEL28 cells were used as positive controls. As shown in Fig. 3, α-synuclein was strongly detected in MeWo and SK-MEL28 cells and weakly detected in WM266-4 cells, whereas it was undetectable in A-375 cells. Interestingly, both MeWo and SK-MEL28 were also positive for the melanosome-related marker proteins MART-1 and HMB-45, but A-375 was negative for them. WM266-4 was weakly positive for MART-1 and negative for HMB-45. These results suggest that α-synuclein is involved in melanosomes or melanogenesis.


Parkinson's disease-related protein, alpha-synuclein, in malignant melanoma.

Matsuo Y, Kamitani T - PLoS ONE (2010)

Expression levels of α-synuclein in human melanoma cell lines.Expression of endogenous α-synuclein was examined in melanoma cell lines by Western blotting using mouse monoclonal anti-α-synuclein antibody 4D6. Total cell lysates of HeLa cells expressing FLAG-tagged α-synuclein and SK-MEL28 cells were loaded as positive controls. To demonstrate expression of melanoma markers, we performed Western blotting using monoclonal antibodies against MART-1 and HMB-45. To demonstrate equal loading amounts of total cell lysates, Western blotting using anti-actin antibody was also performed (bottom panel). The detected proteins are indicated on the right. Molecular size markers are shown in kilodaltons.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864738&req=5

pone-0010481-g003: Expression levels of α-synuclein in human melanoma cell lines.Expression of endogenous α-synuclein was examined in melanoma cell lines by Western blotting using mouse monoclonal anti-α-synuclein antibody 4D6. Total cell lysates of HeLa cells expressing FLAG-tagged α-synuclein and SK-MEL28 cells were loaded as positive controls. To demonstrate expression of melanoma markers, we performed Western blotting using monoclonal antibodies against MART-1 and HMB-45. To demonstrate equal loading amounts of total cell lysates, Western blotting using anti-actin antibody was also performed (bottom panel). The detected proteins are indicated on the right. Molecular size markers are shown in kilodaltons.
Mentions: α-Synuclein protein is highly expressed in the human malignant melanoma SK-MEL28 cell line, suggesting that it may be expressed in other melanoma cell lines. To test this possibility, we examined the expression levels of α-synuclein and two melanoma markers (MART-1 and HMB-45) in 3 other malignant melanoma cell lines, A-375, MeWo, and WM266-4, by Western blotting. HeLa cell transfectants expressing FLAG-tagged α-synuclein and SK-MEL28 cells were used as positive controls. As shown in Fig. 3, α-synuclein was strongly detected in MeWo and SK-MEL28 cells and weakly detected in WM266-4 cells, whereas it was undetectable in A-375 cells. Interestingly, both MeWo and SK-MEL28 were also positive for the melanosome-related marker proteins MART-1 and HMB-45, but A-375 was negative for them. WM266-4 was weakly positive for MART-1 and negative for HMB-45. These results suggest that α-synuclein is involved in melanosomes or melanogenesis.

Bottom Line: However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi.Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Center for Molecular Chaperone/Radiobiology and Cancer Virology, Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.

ABSTRACT

Background: Melanoma is the major cause of skin cancer death worldwide. Parkinson's disease is a neurodegenerative disorder that is caused by mutation of alpha-synuclein or other genes. Importantly, epidemiological studies have reported co-occurrence of melanoma and Parkinson's disease, suggesting that these two diseases could share common genetic components.

Methodology/principal findings: Recently, we found that human melanoma cell lines highly express alpha-synuclein, whereas the protein is undetectable in the non-melanoma cancer cell lines tested. To investigate the expression of alpha-synuclein in human melanoma tissues, we immunostained sections of melanoma, nevus, non-melanocytic cutaneous carcinoma, and normal skin. alpha-Synuclein was positively detected in 86% of the primary and 85% of the metastatic melanoma sections, as well as in 89% of nevus sections. However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.

Conclusions/significance: The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi. Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

Show MeSH
Related in: MedlinePlus