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The A3 adenosine receptor is highly expressed in tumor versus normal cells: potential target for tumor growth
Lea Madi1, Avivit Ochaion, Lea Rath-Wolfson
1Can-Fite BioPharma Ltd., Kiryat-Matalon, Petach-Tikva, Israel.
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 kappaB 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 kappaB 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.
Insights
The adenosine A(3) receptor (A(3)AR) is highly expressed in primary and metastatic solid tumors. This suggests A(3)AR is a potential target for inhibiting tumor growth by down-regulating key cell proliferation factors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Adenosine A(3) receptor (A(3)AR) activation inhibits tumor cell growth by down-regulating nuclear factor kappaB and cyclin D1.
- Investigating A(3)AR expression levels in tumor versus normal tissues is crucial to determine its potential as a specific therapeutic target.
Purpose of the Study:
- To survey A(3)AR expression in various tumor tissues compared to adjacent normal cells.
- To evaluate the potential of A(3)AR as a specific target for tumor growth inhibition.
Main Methods:
- Reverse transcription-PCR analysis of A(3)AR mRNA in paraffin-embedded tumor tissues and adjacent normal tissues or lymph node metastasis.
- Western blot analysis of A(3)AR protein expression in fresh tumor samples and correlation with adjacent normal tissue.
Main Results:
- A(3)AR mRNA expression was significantly higher in colon and breast carcinoma tissues compared to adjacent normal tissues.
- Lymph node metastasis exhibited even higher A(3)AR mRNA levels than primary tumor tissue.
- Protein analysis confirmed higher A(3)AR expression in 61% of colon and 78% of breast tumors versus adjacent normal tissue, associated with elevated nuclear factor kappaB and cyclin D1.
Conclusions:
- High A(3)AR expression is a characteristic of both primary and metastatic solid tumors.
- These findings, coupled with previous data, strongly support A(3)AR as a promising target for developing novel anti-tumor therapies.
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