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P2X(7) receptor expression is decreased in epithelial cancer cells of ectodermal, uro-genital sinus, and distal
Xin Li1, Xiaoping Qi, Lingyin Zhou
1Department of Pathology, University of Toledo Medical Center, 3000 Arlington Avenue, Toledo, OH, 43614, USA, xin.li@utoledo.edu.
Abstract:
The P2X(7) receptor is an important regulator of epithelial cell growth. The aim of the present study was to better understand the biological significance of P2X(7) receptor expression in normal and cancer human epithelial tissues. P2X(7) receptor and messenger RNA (mRNA) levels were determined in human tissues containing epithelial dysplastic, pre- or early cancerous, and cancer cells, and the levels were compared to those in the corresponding normal epithelial cells within the same tissue of the same case. P2X(7) receptor levels were determined by quantification of immunoreactivity specific to the functional (full-length) P2X(7) receptor, and P2X(7) mRNA levels were determined by real-time polymerase chain reaction. P2X(7) receptor levels in cancer cells were similar (colon adenocarcinoma) or greater (thyroid papillary carcinoma) than those in the corresponding normal cells. In contrast, in cancer cells of the ectocervix (squamous), endocervix and endometrium (adenocarcinoma), urinary bladder (transitional cell carcinoma), and breast (ductal and lobular adenocarcinomas), P2X(7) receptor levels were lower by about twofold than those in the corresponding normal epithelial cells. Similarly, P2X(7) mRNA levels were lower in uterine, bladder, and breast cancer epithelial tissues by about fourfold than those in the corresponding normal tissues. In addition, P2X(7) receptor levels were decreased already in dysplastic ectocervical cells and pre- or early cancerous endometrial and bladder cells. The data suggest that in epithelia originating from the ectoderm, the uro-genital sinus, and the distal paramesonephric duct, decreased expression of the P2X(7) receptor precedes or coincides with neoplastic changes in those tissues.
Insights
The P2X(7) receptor, crucial for epithelial cell growth, shows decreased expression in various cancers, even preceding neoplastic changes. This finding highlights its potential role in epithelial cancers.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The P2X(7) receptor plays a role in regulating epithelial cell growth.
- Understanding P2X(7) receptor expression is vital in normal and cancerous human epithelial tissues.
Purpose of the Study:
- To investigate the biological significance of P2X(7) receptor expression in human epithelial tissues.
- To compare P2X(7) receptor and mRNA levels in normal, dysplastic, and cancerous epithelial cells.
Main Methods:
- Quantification of immunoreactivity for functional P2X(7) receptor.
- Real-time polymerase chain reaction for P2X(7) mRNA levels.
- Comparison of P2X(7) levels in matched normal and cancerous tissues.
Main Results:
- P2X(7) receptor levels were similar or higher in colon and thyroid cancers compared to normal cells.
- P2X(7) receptor levels were significantly lower in ectocervix, endometrium, bladder, and breast cancers.
- P2X(7) mRNA levels were reduced in uterine, bladder, and breast cancers.
- Decreased P2X(7) receptor expression was observed in early dysplastic and pre-cancerous lesions.
Conclusions:
- Reduced P2X(7) receptor expression precedes or coincides with neoplastic changes in ectoderm, uro-genital sinus, and distal paramesonephric duct epithelia.
- P2X(7) receptor downregulation may serve as an early indicator in specific epithelial cancers.
