scholarly journals Proteomic Study of HPV-Positive Head and Neck Cancers: Preliminary Results

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Géraldine Descamps ◽  
Ruddy Wattiez ◽  
Sven Saussez

Human papillomavirus (HPV) was recently recognized as a new risk factor for head and neck squamous cell carcinoma. For oropharyngeal cancers, an HPV+ status is associated with better prognosis in a subgroup of nonsmokers and nondrinkers. However, HPV infection is also involved in the biology of head and neck carcinoma (HNC) in patients with a history of tobacco use and/or alcohol consumption. Thus, the involvement of HPV infection in HN carcinogenesis remains unclear, and further studies are needed to identify and analyze HPV-specific pathways that are involved in this process. Using a quantitative proteomics-based approach, we compared the protein expression profiles of two HPV+ HNC cell lines and one HPV− HNC cell line. We identified 155 proteins that are differentially expressed (P<0.01) in these three lines. Among the identified proteins, prostate stem cell antigen (PSCA) was upregulated and eukaryotic elongation factor 1 alpha (EEF1α) was downregulated in the HPV+ cell lines. Immunofluorescence and western blotting analyses confirmed these results. Moreover, PSCA and EEF1αwere differentially expressed in two clinical series of 50 HPV+ and 50 HPV− oral cavity carcinomas. Thus, our study reveals for the first time that PSCA and EEF1αare associated with the HPV-status, suggesting that these proteins could be involved in HPV-associated carcinogenesis.

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1069
Author(s):  
Eva-Leonne Göttgens ◽  
Marleen Ansems ◽  
William P. J. Leenders ◽  
Johan Bussink ◽  
Paul N. Span

To study head and neck squamous cell carcinomas (HNSCC) in vitro, a large variety of HNSCC cell lines have been developed. Here, we characterize a panel of 22 HNSCC cell lines, thereby providing a tool for research into tumor-specific treatment options in HNSCC. Both human papillomavirus (HPV) positive and HPV negative tumor cell lines were collected from commercial and collaborative sources. Short tandem repeat profiling was used to confirm or characterize the identity of the cell lines. Targeted sequencing was performed using a standard pathology single molecule Molecular Inversion Probe panel to detect mutations for 23 tumor suppressors and oncogenes. HPV status, p16 status, radiosensitivity data, and hypoxia data are summarized from all cell lines. We detected HPV transcripts in five cell lines, all of which overexpressed p16. One HPV negative cell line was also p16 positive. We detected mutations in KIT (SCCNij185), PIK3CA (SCCNij185), and CDKN2A (UT-SCC-5 and UT-SCC-38). TP53 mutations were the most frequent, occurring in 16/22 cell lines. HPV infection and TP53 mutations were almost mutually exclusive, with the exception of 93-VU-147T. The cell lines exhibited a wide range of sensitivities towards hypoxia and irradiation. Here, we provide a description of a set of frequently used HNSCC cell lines with diverse characteristics as found in HNSCC patients.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Koji Kitamura ◽  
Keisuke Nimura ◽  
Rie Ito ◽  
Kotaro Saga ◽  
Hidenori Inohara ◽  
...  

AbstractHuman papillomavirus (HPV) 16 infection in the oropharynx is one of the major risk factors for oropharyngeal carcinoma. Although the HPV E6 and E7 proteins are known to have a role in head and neck carcinogenesis, whether their expression is maintained once the tumour has developed still remains unclear. We evaluated the expression of these proteins in HPV16-positive cancer cell lines and clinical oropharyngeal specimens. Two out of the four commercially available antibodies directed against the E7 protein could detect the E7 protein overexpressed in the 293FT cells, human embryonic kidney cells, although none of the four commercially available anti-E6 antibodies could detect the overexpressed E6 protein. Whereas HPV16-positive head and neck or cervical carcinoma cell lines expressed the E7 mRNA, the antibodies with an ability to detect the E7 protein could not detect it in western blotting in these HPV16-positive cell lines. In clinical specimens, E7 protein was partially detected in p16-positive area in p16-positive and HPV16 DNA-positive samples, but not in p16-negative and HPV DNA-negative or p16-positive and HPV DNA-negative samples. Consistent with these findings, the E7 protein was poorly translated from the endogenous structure of the E7 mRNA, although significant E7 mRNA expression was detected in these samples. Our findings indicate that E7 protein is partially expressed in p16-positive area in p16-positive and HPV16 DNA-positive clinical specimens.


2021 ◽  
Vol 12 ◽  
Author(s):  
Pengfei Li ◽  
Zhifang Hao ◽  
Jingyu Wu ◽  
Chen Ma ◽  
Yintai Xu ◽  
...  

Macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2) in the immune system, performing pro-inflammatory and anti-inflammatory functions, respectively. Human THP-1 and mouse RAW264.7 cell line models have been widely used in various macrophage-associated studies, while the similarities and differences in protein expression profiles between the two macrophage models are still largely unclear. In this study, the protein expression profiles of M1 and M2 phenotypes from both THP-1 and RAW264.7 macrophages were systematically investigated using mass spectrometry-based proteomics. By quantitatively analyzing more than 5,000 proteins among different types of macrophages (M0, M1 and M2) from both cell lines, we identified a list of proteins that were uniquely up-regulated in each macrophage type and further confirmed 43 proteins that were commonly up-regulated in M1 macrophages of both cell lines. These results revealed considerable divergences of each polarization type between THP-1 and RAW264.7 macrophages. Moreover, the mRNA and protein expression of CMPK2, RSAD2, DDX58, and DHX58 were strongly up-regulated in M1 macrophages for both macrophage models. These data can serve as important resources for further studies of macrophage-associated diseases in experimental pathology using human and mouse cell line models.


2019 ◽  
Vol 111 (9) ◽  
pp. 970-982 ◽  
Author(s):  
Sabine Heitzeneder ◽  
Elena Sotillo ◽  
Jack F Shern ◽  
Sivasish Sindiri ◽  
Peng Xu ◽  
...  

AbstractBackgroundEwing sarcoma (EWS) manifests one of the lowest somatic mutation rates of any cancer, leading to a scarcity of druggable mutations and neoantigens. Immunotherapeutics targeting differentially expressed cell surface antigens could provide therapeutic benefit for such tumors. Pregnancy-associated plasma protein A (PAPP-A) is a cell membrane-associated proteinase produced by the placenta that promotes fetal growth by inducing insulinlike growth factor (IGF) signaling.MethodsBy comparing RNA expression of cell surface proteins in EWS (n = 120) versus normal tissues (n = 42), we comprehensively characterized the surfaceome of EWS to identify highly differentially expressed molecules. Using CRISPR/Cas-9 and anti-PAPP-A antibodies, we investigated biological roles for PAPP-A in EWS in vitro and in vivo in NSG xenograft models and performed RNA-sequencing on PAPPA knockout clones (n = 5) and controls (n = 3). All statistical tests were two-sided.ResultsEWS surfaceome analysis identified 11 highly differentially overexpressed genes, with PAPPA ranking second in differential expression. In EWS cell lines, genetic knockout of PAPPA and treatment with anti-PAPP-A antibodies revealed an essential survival role by regulating local IGF-1 bioavailability. MAb-mediated PAPPA inhibition diminished EWS growth in orthotopic xenografts (leg area mm2 at day 49 IgG2a control (CTRL) [n = 14], mean = 397.0, SD = 86.1 vs anti-PAPP-A [n = 14], mean = 311.7, SD = 155.0; P = .03; median OS anti-PAPP-A = 52.5 days, 95% CI = 46.0 to 63.0 days vs IgG2a = 45.0 days, 95% CI = 42.0 to 52.0 days; P = .02) and improved the efficacy of anti-IGF-1R treatment (leg area mm2 at day 49 anti-PAPP-A + anti-IGF-1R [n = 15], mean = 217.9, SD = 148.5 vs IgG2a-CTRL; P < .001; median OS anti-PAPP-A + anti-IGF1R = 63.0 days, 95% CI = 52.0 to 67.0 days vs IgG2a-CTRL; P < .001). Unexpectedly, PAPPA knockout in EWS cell lines induced interferon (IFN)-response genes, including proteins associated with antigen processing/presentation. Consistently, gene expression profiles in PAPPA-low EWS tumors were enriched for immune response pathways.ConclusionThis work provides a comprehensive characterization of the surfaceome of EWS, credentials PAPP-A as a highly differentially expressed therapeutic target, and discovers a novel link between IGF-1 signaling and immune evasion in cancer, thus implicating shared mechanisms of immune evasion between EWS and the placenta.


2019 ◽  
Vol 96 (3) ◽  
pp. 652-657 ◽  
Author(s):  
David Kessel ◽  
Won Jin Cho ◽  
Joseph Rakowski ◽  
Harold E. Kim ◽  
Hyeong‐Reh C. Kim

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13566-e13566
Author(s):  
N Mullai ◽  
Soleiman Osman ◽  
Joseph Rattenni

e13566 Background: Human papilloma virus (HPV) is the most common sexually transmitted agent and has extensive association with many malignancies such as cervical, vaginal, vulvar, penile, and head and neck cancers. Vaccination helps prevent sexually transmitted diseases due to HPV. In addition, it provides protection against cancers caused by persistent, high-risk HPV infection in both male and female. Methods: Data collected from the medical records of patients diagnosed with anogenital, and head and neck cancers during 2017-2019 were studied retrospectively and the association of HPV infection was analyzed. Results: There were thirty-three cases of anogenital, and head and neck cancers diagnosed during the study period. The following were the occurrences: penile cancer 1, anal cancer 4, cervical/uterine/vaginal cancers 10, and head and neck cancer including tonsil, base of tongue, vocal cord, and glottis 18. HPV status was available in twenty-six (79%) patients. Fourteen patients were positive for high-risk 16/18 HPV strain, twelve were HPV negative, and HPV status was unknown for seven patients. Most of the patients were smokers and none of them had received HPV vaccination. The patients were treated appropriately with chemotherapy, radiation, and surgery. Conclusions: Human papilloma virus (HPV) infection type 16/18 is the most common sexually transmitted infection associated with significant anogenital and head and neck cancers.Vaccinations protect against persistent, high-risk HPV infection that may lead to malignancies. However, the HPV vaccination initiation and completion rates are only 41.7% and 21.6% respectively in males, and 60% and 39.7% respectively in females. The lack of opportunity does not appear to be a major reason for this low coverage. Some of the barriers for low adoption of HPV vaccination were concern about vaccine safety (70%), lack of knowledge about HPV related diseases (56%), very young to vaccinate (56%), fear of riskier sexual behavior (56%), and reluctance as not being included in the required immunization schedule (71%). In addition, several people refused HPV vaccination due to misinformation in social media. The primary purpose of HPV vaccination is to help prevent sexually transmitted diseases. Further, such vaccination can also prevent several cancers caused by persistent infection. Therefore, HPV vaccination has the potential to eliminate such risk if enforced at a young age in school. The above study and data stress this role and the importance of public awareness of the HPV vaccine as a cancer prevention agent.


2013 ◽  
Vol 106 ◽  
pp. S42-S43
Author(s):  
M. Téllez-Gabriel ◽  
L.C. Navas ◽  
X. León ◽  
A. López-Pousa ◽  
M. Que ◽  
...  

2016 ◽  
Vol 12 (1) ◽  
pp. 219-232 ◽  
Author(s):  
D. Vergara ◽  
P. Simeone ◽  
S. De Matteis ◽  
S. Carloni ◽  
P. Lanuti ◽  
...  

Classical Hodgkin lymphoma models of T- and B-cell derivation show significant differences in their protein expression profiles.


2007 ◽  
Vol 358 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Nham Tran ◽  
Tessa McLean ◽  
Xiaoying Zhang ◽  
Chuan Jia Zhao ◽  
John Michael Thomson ◽  
...  

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