A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3

Rahman, Nafis; Bennink, Herjan J.T. Coelingh; Chruściel, Marcin; Sharp, Victoria L.; Zimmerman, Yvette; Dina, Roberto; Li, Xiangdong; Ellonen, Antti; Rivero-Müller, Adolfo; Dilworth, S. J.; Ghaem‐Maghami, Sadaf; Vainio, Olli; Huhtaniemi, Ilpo

doi:10.1096/fj.11-192468

Cited by 11 publications

(7 citation statements)

References 47 publications

(72 reference statements)

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“…A recent study ( 10 ) based on correlating expression arrays and array comparative genomic hybridization (CGH) data also found that UBAP2L showed amplification expression in HCC, which is one of the early genomic events associated with HCC development. Naz and Dhandapani ( 11 ) reported that UBAP2L showed 97% homology at the nucleotide and amino acid sequences with ZPC-interacting protein involved in malignant ovarian tumors ( 15 ). Furthermore, Sudhir et al ( 16 ) identified UBAP2L as a novel target of mitogen-activated protein kinase (MAPK) family kinases that acts as a downstream component of Ras-mediated signaling and has an important role in the pathogenesis of certain types of human cancer, such as lung cancer and glioma ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of ubiquitin-associated protein 2-like with a short hairpin RNA inhibits human glioma cell growth in vitro

Zhao¹,

Zong²,

Xie³

et al. 2015

International Journal of Molecular Medicine

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Ubiquitin-associated protein 2-like (UBAP2L), which contains a ubiquitin-associated (UBA) domain near its N-terminus, has been indicated in the pathogenesis of several human cancers, including multiple myeloma, hepatocellular carcinoma and malignant ovarian tumors. However, the role of UBAP2L in human glioma remains unknown. In the present study, UBAP2L was widely expressed in multiple glioma cell lines. To further examine the effects of UBAP2L on glioma growth, lentivirus-mediated short hairpin RNA (shRNA) was employed to knockdown UBAP2L expression in the glioblastoma cell lines. Depletion of UBAP2L significantly inhibited the proliferation and colony formation ability, as determined by MTT and colony formation assays. Cell cycle analysis showed that UBAP2L knockdown induced G0/G1 phase arrest in U251 and U373 cells, while S phase arrest was induced in A172 cells. These results suggest that UBAP2L has a key role in glioma cell growth, and may act as an oncogene to promote malignant glioma development.

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Section: Discussionmentioning

confidence: 99%

Downregulation of ubiquitin-associated protein 2-like with a short hairpin RNA inhibits human glioma cell growth in vitro

Zhao¹,

Zong²,

Xie³

et al. 2015

International Journal of Molecular Medicine

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“…Although ZP3 expression has been found in 100% of normal tissue, it has also been present in 64% of OSCC samples which leads to an exclusion of ZP3 for a good potential cancer-specific biomarker. However, in mice, ZP3 has been used as treatment approach against ovarian cancer based upon immunization against murine ZP3 [ 15 ]. A recent publication deals with ZP3 as new prognostic and potential therapeutic marker in renal clear cell carcinoma showing ZP3 30-fold higher expressed in tumor versus normal counterparts [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…This protein has already been detected in normal and cancerous tissues, particularly investigated in prostate cancer cells [ 14 ]. A treatment strategy in mice for ovarian cancer that is based upon immunization against murine ZP3 has also been published [ 15 ]. All in all, aware of these observations, we consider ZP3 to be a potent candidate for OSCC diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Neoexpression of JUNO in Oral Tumors Is Accompanied with the Complete Suppression of Four Other Genes and Suggests the Application of New Biomarker Tools

Kraus

Weider

Probstmeier

et al. 2022

JPM

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Background. Our study describes the neoexpression (Juno) and suppression (catsperD, dysferlin, Fer1L5 and otoferlin) of selected genes in oral squamous cell carcinomas (OSCCs). As the expression pattern of these genes allows a “yes” or “no” statement by exhibiting an inverse expression pattern in malignant versus benign tissues, they represent potential biomarkers for the characterization of oral malignancies, particularly OSCCs. Methods. Differential expression analyses of selected genes of interest were examined by quantitative PCR of oral cancer tissues compared to normal. Results. Five candidates out of initially nine genes were examined, demonstrating Juno as a putative new tumor marker selectively expressed in OSCCs. Interestingly, the expression of four other genes in benign tissues was completely repressed in tumor tissues with a specificity and sensitivity of 100%. No correlation was observed regarding patients’ sex, tumor staging and grading, and tumor site. Conclusion. The present study shows novel candidates that might be useful tools for oral cancer diagnosis. The neoexpression of Juno in cancerous tissues makes it a promising target molecule regarding its potential in diagnosis as well a therapeutic tool. Moreover, our observations suggest that also the repression of gene expression can be used for diagnosing—at least—OSCCs.

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“…In addition to the expression in female and male gametes under physiological circumstances, ectopic expression of ZP3 has been shown in cancer ( 20 – 22 ). ZP3 protein was abundantly expressed in granulosa cell tumors, a rare form of ovarian cancer, and was unexpectedly shown to localize to the cytoplasm ( 20 ), contradicting the plasma membrane localization and extracellular secretion of ZP3 in oocytes. Also in the prostate cancer cell line PC3, ZP3 protein appeared dominantly cytoplasmic ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

“…While the enriched expression of ZP3 in cancer versus normal tissue provides a therapeutic opportunity, whether ZP3 is secreted from cancer cells or not is an important strategic determinant for the development of a cancer immunotherapy based on active or passive immunization. The proof-of-principle for the development of a ZP3-based cancer vaccine for active immunization has been demonstrated in a transgenic mouse model of ovarian granulosa cell cancer ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

A tumor cell specific Zona Pellucida glycoprotein 3 RNA transcript encodes an intracellular cancer antigen

Schultz,

Zimmerman,

Moelans

et al. 2023

Front. Oncol.

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BackgroundExpression of Zona Pellucida glycoprotein 3 (ZP3) in healthy tissue is restricted to the extracellular Zona Pellucida layer surrounding oocytes of ovarian follicles and to specific cells of the spermatogenic lineage. Ectopic expression of ZP3 has been observed in various types of cancer, rendering it a possible therapeutic target.MethodsTo support its validity as therapeutic target, we extended the cancer related data by investigating ZP3 expression using immunohistochemistry (IHC) of tumor biopsies. We performed a ZP3 transcript specific analysis of publicly available RNA-sequencing (RNA-seq) data of cancer cell lines (CCLs) and tumor and normal tissues, and validated expression data by independent computational analysis and real-time quantitative PCR (qPCR). A correlation between the ZP3 expression level and pathological and clinical parameters was also investigated.ResultsIHC data for several cancer types showed abundant ZP3 protein staining, which was confined to the cytoplasm, contradicting the extracellular protein localization in oocytes. We noticed that an alternative ZP3 RNA transcript, which we term ‘ZP3-Cancer’, was annotated in gene databases that lacks the genetic information encoding the N-terminal signal peptide that governs entry into the secretory pathway. This explains the intracellular localization of ZP3 in tumor cells. Analysis of publicly available RNA-seq data of 1339 cancer cell lines (CCLs), 10386 tumor tissues (The Cancer Genome Atlas) and 7481 healthy tissues (Genotype-Tissue Expression) indicated that ZP3-Cancer is the dominant ZP3 RNA transcript in tumor cells and is highly enriched in many cancer types, particularly in rectal, ovarian, colorectal, prostate, lung and breast cancer. Expression of ZP3-Cancer in tumor cells was confirmed by qPCR. Higher levels of the ZP3-Cancer transcript were associated with more aggressive tumors and worse survival of patients with various types of cancer.ConclusionThe cancer-restricted expression of ZP3-Cancer renders it an attractive tumor antigen for the development of a therapeutic cancer vaccine, particularly using mRNA expression technologies.

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A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3

Cited by 11 publications

References 47 publications

Downregulation of ubiquitin-associated protein 2-like with a short hairpin RNA inhibits human glioma cell growth in vitro

Downregulation of ubiquitin-associated protein 2-like with a short hairpin RNA inhibits human glioma cell growth in vitro

Neoexpression of JUNO in Oral Tumors Is Accompanied with the Complete Suppression of Four Other Genes and Suggests the Application of New Biomarker Tools

A tumor cell specific Zona Pellucida glycoprotein 3 RNA transcript encodes an intracellular cancer antigen

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