MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Natural killer (NK) cells are an important resource of the innate immune system directly involved in the spontaneous recognition and lysis of virus-infected and tumor cells. An exquisite balance of inhibitory and activating receptors tightly controls the NK cell activity. At present, one of the best-characterized activating receptors is NKG2D, which promotes the NK-mediated lysis of target cells by binding to a family of cell surface ligands encoded by the MHC class I chain-related (MIC) genes, among others. The goal of this study was to describe the expression pattern of MICA and MICB at the molecular and cellular levels in human cervical cancer cell lines infected or not with human papillomavirus, as well as in a non-tumorigenic keratinocyte cell line.</p> <p>Results</p> <p>Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress.</p> <p>Conclusions</p> <p>This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.</p

Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is the second most common cancer in women worldwide. NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Increased serum levels of MICA have been found in patients with epithelial tumors. The aim of this study was to compare the levels of soluble MICA (sMICA) and NKG2D-expressing NK and T cells in blood samples from patients with cervical cancer or precursor lesions with those from healthy donors.</p> <p>Methods</p> <p>Peripheral blood with or without heparin was collected to obtain mononuclear cells or sera, respectively. Serum sMICA levels were measured by ELISA and NKG2D-expressing immune cells were analyzed by flow cytometry. Also, a correlation analysis was performed to associate sMICA levels with either NKG2D expression or with the stage of the lesion.</p> <p>Results</p> <p>Significant amounts of sMICA were detected in sera from nearly all patients. We found a decrease in the number of NKG2D-expressing NK and T cells in both cervical cancer and lesion groups when compared to healthy donors. Pearson analysis showed a negative correlation between sMICA and NKG2D-expressing T cells; however, we did not find a significant correlation when the analysis was applied to sMICA and NKG2D expression on NK cells.</p> <p>Conclusion</p> <p>Our results show for the first time that high sMICA levels are found in sera from patients with both cervical cancer and precursor lesions when compared with healthy donors. We also observed a diminution in the number of NKG2D-expressing NK and T cells in the patient samples; however, a significant negative correlation between sMICA and NKG2D expression was only seen in T cells.</p

SMICA levels and the number of NKG2D-expressing T cells are negatively correlated

Correlation analysis was done using the Pearson test. Values are normalized as log.<p><b>Copyright information:</b></p><p>Taken from "Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions"</p><p>http://www.biomedcentral.com/1471-2407/8/16</p><p>BMC Cancer 2008;8():16-16.</p><p>Published online 21 Jan 2008</p><p>PMCID:PMC2270854.</p><p></p

The number of NKG2D-expressing NK and T cells diminishes during cervical cancer progression

NKG2D expression was measured using flow cytometry while gating on CD56CD3(NK cell) and CD56CD3(T cell) populations. The histograms and dot plots show the results obtained from a representative individual of each group. The same tendency is observed in both NK and T cells (filled curve: isotype control Ab, open curve: anti-NKG2D).<p><b>Copyright information:</b></p><p>Taken from "Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions"</p><p>http://www.biomedcentral.com/1471-2407/8/16</p><p>BMC Cancer 2008;8():16-16.</p><p>Published online 21 Jan 2008</p><p>PMCID:PMC2270854.</p><p></p

NKG2D-expressing immune cells are decreased in patients with cervical cancer and precursor lesions

Three color flow cytometry analysis to detect CD3, CD56 and NKG2D was carried out on PBMC to determine the percentage of NKG2D-positive cells. NKG2D-expressing NK cells (CD56CD3population); NKG2D-expressing T cells (CD56CD3population). The box plots represent each study group. Medians are represented as thick horizontal lines, 25and 75percentiles as boxes and 10and 90percentiles as whiskers. *Extreme values.<p><b>Copyright information:</b></p><p>Taken from "Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions"</p><p>http://www.biomedcentral.com/1471-2407/8/16</p><p>BMC Cancer 2008;8():16-16.</p><p>Published online 21 Jan 2008</p><p>PMCID:PMC2270854.</p><p></p