Purpose: A 3 adenosine receptor (A 3 AR) activation was shown to inhibit the growth of various tumor cells via the down-regulation of nuclear factor B and cyclin D1. To additionally elucidate whether A 3 AR is a specific target, a survey of its expression in tumor versus adjacent normal cells was conducted.Experimental Design: A 3 AR mRNA expression in various tumor tissues was tested in paraffin-embedded slides using reverse transcription-PCR analysis. A comparison with A 3 AR expression in the relevant adjacent normal tissue or regional lymph node metastasis was performed. In addition, A 3 AR protein expression was studied in fresh tumors and was correlated with that of the adjacent normal tissue.Results: Reverse transcription-PCR analysis of colon and breast carcinoma tissues showed higher A 3 AR expression in the tumor versus adjacent non-neoplastic tissue or normal tissue. Additional analysis revealed that the lymph node metastasis expressed even more A 3 AR mRNA than the primary tumor tissue. Protein analysis of A 3 AR expression in fresh tumors derived from colon (n ؍ 40) or breast (n ؍ 17) revealed that 61% and 78% had higher A 3 AR expression in the tumor versus normal adjacent tissue, respectively. The high A 3 AR expression level in the tumor tissues was associated with elevated nuclear factor B and cyclin D1 levels. High A 3 AR mRNA expression was also demonstrated in other solid tumor types.Conclusions: Primary and metastatic tumor tissues highly express A 3 AR indicating that high receptor expression is a characteristic of solid tumors. These findings and our previous data suggest A 3 AR as a potential target for tumor growth inhibition.
SUMMARYVitiligo is considered an autoimmune disorder due to the generation and presence of autoantibodies directed against melanocyte antigens in the patients' sera. In the present study we point towards a newly defined autoantigen in vitiligo, the enzyme tyrosinase, which participates in the process of melanogenesis. Anti-tyrosinase antibodies were detected in the sera of seven patients with diffuse and 11 patients with localized vitiligo. Employing solid-phase ELISA to mushroom tyrosinase, we found that patients with diffuse vitiligo had significantly higher titres of IgG anti-tyrosinase autoantibodies than patients with localized disease or healthy subjects. These anti-tyrosinase autoantibodies have relatively high functional affinity to tyrosinase and can be recovered from vitiligo patients' sera by affinity purification. The anti-tyrosinase antibodies do not cross-react with other enzymes recognized as autoantigens in different autoimmune disorders and the autoantibodies do not block the enzymatic activity of tyrosinase, indicating that they are not reacting with the catalytic site of the enzyme. These data point to tyrosinase as an autoantigen in vitiligo and suggest that anti-tyrosinase titres can serve as a marker for disease activity.
BACKGROUND Tyrosinase is an enzyme that participates in the process of melanin production in normal melanocytes and melanoma cells. Enzymes are known to be autoantigens in various autoimmune disorders; thus, after the detection of antityrosinase antibodies in patients with vitiligo and melanoma, tyrosinase was defined as an autoantigen in these conditions. In some patients with melanoma the disease is associated with the appearance of "vitiligo‐like" white patches on the skin, called melanoma‐associated hypopigmentation (MAH). In this article, the authors summarize the recent data related to antityrosinase antibodies and expand on their role in the pathogenesis of vitiligo, melanoma, and MAH. In addition, the beneficial clinical applications of antityrosinase antibodies are presented. METHODS An enzyme‐linked immunoadsorbent assay to detect the antityrosinase antibodies in the serum of patients and healthy volunteers was established using mushroom tyrosinase. Employing this method, antityrosinase antibodies were analyzed in a diverse group of patients with melanoma and vitiligo and in mice immunized with tyrosinase. RESULTS In patients with melanoma, those with metastatic disease had a higher titer of antityrosinase antibodies compared with healthy subjects, whereas patients with MAH and those with no evidence of disease had similar titers to the control group. The titer of antityrosinase antibodies in patients with metastatic melanoma treated by vaccination with antiidiotypic antibodies mimicking the high molecular weight melanoma‐associated antigen (HMW MAA) initially increased after the vaccination and then decreased. High titers of antityrosinase antibodies were detected in patients with diffuse vitiligo compared with patients with localized disease and with the healthy control group. Mice immunized with tyrosinase generated a high titer of antityrosinase antibodies and after the inoculation of melanoma cells developed a lower number of lung metastases compared with an unvaccinated control group. CONCLUSIONS The appearance of antityrosinase autoantibodies in the serum of patients with metastatic melanoma and diffuse vitiligo is characterized by these two pathologies. The changes in the serum level of these autoantibodies in patients with melanoma after immunization with another antigen (HMW MAA) may have diagnostic and therapeutic implications. Cancer 1997; 79:1461‐4. © 1997 American Cancer Society.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.