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

Abstract

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.

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

“…It is reported that the skeletal muscle microenvironment reduces cancer cell tumorigenicity and elicits paracrine-mediated cytotoxic and cytostatic responses from metastatic cancer cells (30). In particular, several studies identified the A 3 adenosine receptor (A 3 AR), which is expressed by multiple cancer cell types (31), as key in the antimetastatic and protective effect of skeletal muscle cells (32). Before investigating the role of A 3 AR in extravasation, we first demonstrated through immunofluorescence that BOKL introduced in our system expressed the A 3 AR (Fig.…”

An in vivo model of melanoma: treatment with ATP

“…These antitumour effects might be counteracted to some extent by adenosine, produced after breakdown of ATP by ectonucleotidase, which is known to promote proliferation of tumour cells, as well as acting as an immunosuppressant [32][33][34][35][36]. However, adenosine has also been shown to have anti-tumour effects by inhibiting tumour growth via A 3 receptors [37][38][39] or by inhibiting apoptosis [40]. Further studies are needed to resolve these contradictory issues.…”

Bioinformatics construction of the human cell surfaceome

“…Another interesting gene, SMO, is a known oncogene for basal cell carcinoma (14) that activates the Hedgehog pathway, leading to an increase in angiogenic factors (15), cyclins D1 and B1 (16), and antiapoptotic genes, and a decrease in apoptotic genes (FAS) (17). In addition, ADORA3, an adenosine receptor, has been observed to be highly expressed in a variety of tumors and has been suggested as a potential therapeutic target (18).…”