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The A₃ Adenosine Receptor Is Highly Expressed in Tumor versus Normal Cells

Potential Target for Tumor Growth Inhibition

¹ Can-Fite BioPharma Ltd., Kiryat-Matalon, Petach-Tikva; Departments of ² Pathology and ³ Surgery, A/B Rabin Medical Center, Campus Golda, Sackler Faculty of Medicine Tel-Aviv University, Petach-Tikva; and ⁴ Unit of Bone and Soft Tissue Oncology, Division of Oncology, The Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel

Purpose: A₃ adenosine receptor (A₃AR) 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 A₃AR is a specific target, a survey of its expression in tumor versus adjacent normal cells was conducted.

Experimental Design: A₃AR mRNA expression in various tumor tissues was tested in paraffin-embedded slides using reverse transcription-PCR analysis. A comparison with A₃AR expression in the relevant adjacent normal tissue or regional lymph node metastasis was performed. In addition, A₃AR 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 A₃AR expression in the tumor versus adjacent non-neoplastic tissue or normal tissue. Additional analysis revealed that the lymph node metastasis expressed even more A₃AR mRNA than the primary tumor tissue. Protein analysis of A₃AR expression in fresh tumors derived from colon (n = 40) or breast (n = 17) revealed that 61% and 78% had higher A₃AR expression in the tumor versus normal adjacent tissue, respectively. The high A₃AR expression level in the tumor tissues was associated with elevated nuclear factor B and cyclin D1 levels. High A₃AR mRNA expression was also demonstrated in other solid tumor types.

Conclusions: Primary and metastatic tumor tissues highly express A₃AR indicating that high receptor expression is a characteristic of solid tumors. These findings and our previous data suggest A₃AR as a potential target for tumor growth inhibition.

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