Some remarks on the somatic expression of sperm protein 17

Abstract

Dear Sir,We read with interest the article by Straughn et al.,"Expression of sperm protein 17 (Sp17) in ovarian cancer". 1 Although this study is a significant contribution to the field of cancer research, the following observations need to be made.Sperm protein 17 (Sp17) is a highly conserved mammalian protein detected in mouse, monkey, baboon, macaque and human (HSp17) testis and spermatozoa. Using a pair of sequence-specific primers, the presence of HSp17 mRNA has been clearly shown in 17% of patients with multiple myeloma and in the primary tumor cells from 70% of patients with ovarian carcinoma. 2-4 Chiriva-Internati et al. 5 have further shown that HSp17 contains functional cytotoxic T-lymphocyte epitopes. These results indicate that HSp17 is a cancer-testis (CT) antigen in multiple myeloma and ovarian carcinoma and suggest its suitability as a target for immunotherapy of these 2 neoplastic diseases.CT antigens constitute a group of proteins expressed in histologically different types of neoplasia and whose expression in normal tissues is limited to germ cells of the testis, with occasional expression in female reproductive organs. 6,7 Although Sp17 has been frequently reported to be expressed solely in the testis, transcripts have recently been detected in murine somatic tissues by RT-PCR, albeit in much lower amounts when compared to testis. 8 Despite Lim et al. 4 having failed to detect mRNA encoding HSp17 in human somatic tissues other than the testis, Frayne and Hall 9 have clearly detected HSp17 transcripts of the predicted size in a panel of human cDNAs including the brain, heart, kidney, liver, lung, pancreas, placenta and testis.In clinical materials, the expression of CT antigens has mostly been studied at the level of gene expression by RT-PCR. However the information provided by this approach is limited because of the impossibility of quantifying cancer cells that are positive for CT antigens. 7,10 On the contrary, by means of specific antibodies it is possible to recognize the presence of the antigen within examined tissues, highlighting not only the quantity but also the type of cells immunopositive for that antigen.By using self-produced mouse anti-HSp17 antibodies, normal human seminiferous tubules were highly positive for HSp17 as well as the flagella of the ejaculated spermatozoa. 11 Since the flagella of spermatozoa are similar to cilia, we then investigated whether HSp17 was identifiable in human ciliated epithelia. We detected a strong presence of HSp17 in ciliated epithelia of the respiratory airways and both the male and female reproductive system. 12 These data extend recent reports in which a proteomic analysis of human airways cilia revealed the expression of HSp17 13 and in which a RT-PCR analysis from a panel of human cDNAs showed HSp17 transcripts in all human tissues examined, including lung and other organs that contain different amounts of ciliated cells. 9 Since cilia have been adapted as versatile tools for many biological processes, such as left-right axis pattern formati...

Limited SP17 expression within tumors diminishes its therapeutic potential

“…Further staining of a large panel of normal human tissues showed SP17 expression in the spermatozoa of the testis and ciliated epithelial cells lining the trachea and uterus (Figure ). These results are in accordance with the previous reports using different SP17 antibodies , confirming the specificity of the antibody. We next investigated the expression of SP17 in 226 tumors of different origin.…”

“…SP17 has been reported in malignancies of different histological origin, including multiple myeloma, cancers of the female reproductive system, esophageal cancer and nervous system tumors , and consequently the protein was included in the group of cancer/testis antigens. However, more recent results have showed SP17 expression in various ciliated human epithelial cells , indicating that SP17 is not a ‘true’ cancer/testis antigen. Despite its expression in non‐germline cells, SP17 has been shown to be highly immunogenic.…”

Enhanced Electrochemical Biosensing of the Sp17 Cancer Biomarker in Serum Samples via Engineered Two-Dimensional MoS2 Nanosheets on the Reduced Graphene Oxide Interface

“… In healthy tissues, Sp17 performs a critical role in increasing the heparin sulfate-mediated adhesion among cells and regulating the interaction of sperm with the zona pellucida during conception . Sp17 expresses itself seldom in normal tissue, with the exception of male spermatozoa, and very weakly in ciliated epithelium cells and embryonic germinal cells, , whereas it expresses itself abundantly in cancer . Recent investigations have suggested that Sp17 was abnormally expressed in a variety of malignant tumors such as esthesioneuroblastomas, esophageal squamous cell carcinomas, ovarian cancers, multiple myelomas, and numerous histological variants associated with human nervous system (NS) malignancies, which include meningeal and neuroectodermal tumors. , In normal human beings, the serum Sp17 concentration has been recorded up to 64–2400 pg mL –1 , whereas in various types of cancer patients, the serum Sp17 concentration is found to be more than 6000 pg mL –1 .…”

Sperm Protein 17 Expression by Murine Epithelial Ovarian Cancer Cells and Its Impact on Tumor Progression

“…Several studies have suggested roles in cell migration, drug resistance, and metastasis [ 11 ], and Sp17 expression is correlated with chemoresistance in clear-cell adenocarcinoma [ 12 ]. Similar to other CTAs, Sp17 displays restricted expression in healthy tissues, except in male spermatozoa, and limited expression in embryonic germinal cells and ciliated epithelia cells [ 13 , 14 ], but displays high expression in cancer [ 15 ]. Moreover, over 90% of vasectomized males develop natural immunity to Sp17, suggesting it as a safe antigenic target for vaccine design [ 16 ].…”