Significance of SHP-1 and SHP-2 Expression in Human Papillomavirus Infected Condyloma acuminatum and Cervical Cancer

Abstract

Human papillomaviruses (HPVs) are a group of DNA viruses that infect the skin and mucous membranes. Type HPV6/11 is closely related to Condyloma acuminatum, while HPV16/18 is the principal cause of cervical cancer. In this study, we examined the expression of protein tyrosine phosphatases SHP-1 and SHP-2 in Condyloma acuminatum, cervical cancer and the relationship between SHP-1/SHP2 expression and HPV infection. Forty Condyloma acuminatum cases, 20 cervical cancer cases and 20 normal human foreskins were examined for HPV infection by in situ hybridization and the expression of SHP-1 and SHP-2 were examined by immunohistochemistry. Results demonstrated that positive expression rates of HPV6/11, HPV16/18, and HPV31/33 were 98%, 10%, and 7.5% in Condyloma acuminatum, 10%, 85%, and 25% in cervical cancer. Only one normal foreskin demonstrated positive staining for HPV16/18. Positive expression rates of SHP-1 and SHP-2 were 80% and 85% in Condyloma acuminatum, 85% and 90% in cervical cancer. The SHP-1 and SHP-2 expressions were mainly distributed in the prickle layer of Condyloma acuminatum and were diffusely distributed in cervical cancer cells. Only 35% and 30% of foreskins demonstrated weak staining in the basal layer cells. There were statistically significant correlations among the infection of HPV and the expression of SHP-1 and SHP-2 in both Condyloma acuminatum and cervical cancer (P < 0.05). SHP-1 expression has a positive correlation with SHP-2 expression. Our results demonstrate putative roles of SHP-1 and SHP-2 in the progression of both Condyloma acuminatum and cervical cancer after HPV infection.

Clinical significance of leukocyte-associated immunoglobulin-like receptor-1 expression in human cervical cancer

“…SHP-1 has been reported to be a negative regulator of angiogenesis (21), and is overexpressed in breast cancer (22). In addition, upregulation of SHP-2 has been found in gastric cancer (23) and HCC (24,25). Cells or tumor stroma can produce collagen (12), and cross-linking LAIR-1 with collagen can phosphatize ITIMs, recruit SHP-1 and SHP-2 (26), and weaken activation signals.…”

SHP2 Is Overexpressed and Inhibits pSTAT1-Mediated APM Component Expression, T-cell Attracting Chemokine Secretion, and CTL Recognition in Head and Neck Cancer Cells

“…These defects appear to be dependent on overexpression of SHP2, an SH2 domain-containing tyrosine phosphatase, which was found to be highly overexpressed in vivo in HNC tumor tissues (Figure 1), compared to surrounding normal epithelium. SHP2 is overexpressed and/or hyperactive in multiple malignancies (12, 13, 29-31), however few studies have investigated their impact on immune cell migration and recognition of tumor cells (32-35). To the best of our knowledge, this is the first report to demonstrate that SHP2 is significantly overexpressed in HNC tissue (Figure 1) with important biological consequences.…”

“…Src homology-2 domain-containing phosphatase (SHP)-2 has been suggested as a negative regulator of the JAK-STAT signal transduction pathway (10, 11) but it has not been implicated in tumor immune escape. Furthermore, SHP2 overexpression and/or hyperactivity have been demonstrated in leukemia, breast, and bladder cancers (12, 13). Thus, we investigated whether overexpression of SHP2 might provide a novel mechanism for CTL escape through dephosphorylation of pSTAT1 in cancer cells, reducing expression of HLA class I APM components as well as pro-inflammatory cytokines and chemokines.…”

<div>Phosphorylation of the viral coat protein regulates RNA virus infection</div>

“…[10][11][12][13] Phosphatases such as Shp1 and Shp2 regulate DNA virus infection as well as signal transduction pathways that can affect innate immune responses. [106][107][108] It is likely that they are also involved in RNA virus infection. It is highly likely that cellular kinases and phosphatases will act on viral CPs as a way to prevent the viral infection process.…”