Expression of Protein Tyrosine Kinases in Head and Neck Squamous Cell Carcinomas

Ongkeko, Weg M.; Altuna, Xabier; Weisman, Robert A.; Wang‐Rodriguez, Jessica

doi:10.1309/btln5wtmj3pcnrrc

Cited by 101 publications

(50 citation statements)

References 17 publications

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“…Five years ago the first study analyzing the expression of c-kit in HNSCC was reported. Ongkeko et al described a significantly higher expression of c-kit in HNSCC compared to benign samples (17). Imatinib was originally designed to inhibit a certain tyrosine kinase in CML (10).…”

Section: Discussionmentioning

confidence: 99%

“…The authors described a significantly higher expression of c-kit in HNSCC compared to benign samples. Surprisingly the expression of c-kit was significantly elevated in carcinomas of the pharynx compared to carcinomas of the larynx (17), but also over 90% of the adenoid cystic carcinomas of the head and neck are c-kit positive. The treatment of adenoid cystic carcinoma primary cultures with imatinib showed a down-regulation of c-kit expression and growth-inhibition (18).…”

Section: Protein-tyrosine Kinases (Ptk)mentioning

confidence: 91%

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Down-regulation of MMP-2 expression due to inhibition of receptor tyrosine kinases by imatinib and carboplatin in HNSCC

Sauter¹

2011

Oncol Rep

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Abstract. Squamous cell carcinoma of the head and neck (HNSCC) is the most common neoplasm arising in the upper aerodigestive tract. Unfortunately, the survival for this type of cancer has not improved significantly in the past 25 years. To enhance the survival rate multimodal therapy regimens have been set up. In these regimens chemotherapy plays a pivotal role in the majority of advanced cases. Transmembrane proteintyrosine kinases (PTK) are fundamental elements of the signal transduction. In consequence, they might be promising targets for cancer therapy. Imatinib (STI 571) was originally designed to inhibit the BCR-ABL tyrosine kinase in chronic myeloid leukemia. But imatinib also has an inhibitory impact on the PTK receptor c-kit and on its PTK activity. Furthermore, growth and invasion of HNSCC are strongly influenced by the extracellular matrix (ECM). The ECM is altered by matrix metalloproteinases (MMP). In this study, we incubated different HNSCC cell lines with rising concentrations of imatinib and/or carboplatin. After an incubation time of up to 10 days, we evaluated c-kit, MMP-2 and MMP-14 by ELISA techniques and immunohistochemical methods. Especially the combination of 7.5 μmol carboplatin with 30 μmol imatinib resulted in a significant decrease in MMP-2 expression in all observed cell lines (p<0.05). We did not demonstrate a significant alteration in c-kit expression by imatinib and carboplatin. We observed an increase in apoptosis in HNSCC cells by the combination of the two observed chemotherapeutic drugs. In all cell lines tested, expression of c-kit and MMP could be demonstrated. Our results indicate that MMP-2 expression was suppressed in the presence of imatinib. Thus, imatinib may exert in part its inhibitory effect on malignant cell growth via the blockage of the signal transduction of PTK receptors. Further studies are warranted, especially one keeping in mind the moderate toxicity of imatinib.

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Section: Discussionmentioning

confidence: 99%

Section: Protein-tyrosine Kinases (Ptk)mentioning

confidence: 91%

Down-regulation of MMP-2 expression due to inhibition of receptor tyrosine kinases by imatinib and carboplatin in HNSCC

Sauter¹

2011

Oncol Rep

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“…Additionally, the practical feedback for extracellular validation was obtained as significant structural indices of polysaccharide components (Tables 1 and 4). On the other hand, the overexpressed performance of some kinases, such as tyrosine protein kinase, is based on the stability of either a de novo managing system [29] or a cellular damage bioplatform [30] and can maintain metabolic balance over an entire process of closed WSMB (Table 2). Furthermore, in order to support the cellular differentiation based on the long-term cultivation bioprocess, the pentose phosphate pathway, e.g., ribose 5-phosphate isomerase, may be activated rather than lignocellulolytic cascades in spite of ligninolytic maximization.…”

Section: Proteomic Evaluation Of Advanced Wsmb Biosystem: Nonspecificmentioning

confidence: 99%

Bioprocess Evaluation of Water Soaking-Based Microbiological Biodegradation with Exposure of Cellulosic Microfibers Relevant to Bioconversion Efficiency

Bak

2015

Appl Biochem Biotechnol

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To verify the interconnective relationship between biodegradation efficiency and microfibril structure, recalcitrant rice straw (RS) was depolymerized using water soaking-based microbiological biodegradation (WSMB). This eco-friendly biosystem, which does not predominantly generate inhibitory metabolites, could increase both the hydrolytic accessibility and fermentation efficiency of RS. In detail, when swollen RS (with Fenton cascades) was simultaneously bio-treated with Phanerochaete chrysosporium for 12 days, the biodegradability was 65.0 % of the theoretical maximum at the stationary phase. This value was significantly higher than the 30.3 % measured from untreated RS. Similarly, the WSMB platform had an effect on the yield enhancement of ethanol productivity of 32.5 %. However, uniform exposure of fibril polymers appeared to have little impact on bioconversion yields. Additionally, the proteomic pools of the WSMB system were analyzed to understand either substrate-specific or nonspecific biocascades based on the change in microcomposite materials. Remarkably, regardless of modified microfibril chains, the significant pattern of 14 major proteins (|fold| > 2) was reasonably analogous in both systems, especially for lignocellulolysis-related targets.

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“…Furthermore literature reports an overexpression of EGFR in 38 -80 % of investigated tumors (Grandis & Tweardy 1993;Ongkeko et al 2005;Bei et al 2004). We noted an overexpression of EGFR mRNA and protein (1.5 fold expression was categorized as an overexpression as compared to NOK) in 48 percent of our cell lines.…”

Section: Paper IImentioning

confidence: 99%

Understanding the Role of EGFR in the Treatment of Head and Neck Squamous Cell Carcinoma

Jedliński¹

2014

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Head and neck squamous cell carcinoma (HNSCC) originates from the epithelial lining of the upper aerodigestive tract. It accounts for over 90 % of the malignancies found in the head and neck region. 600,000 new cases of HNSCC occur each year worldwide. Apart from causing painful lesions, HNSCC directly impacts the patient’s fundamental functions such as breathing and eating and also can disrupt the patient’s senses such as smell, taste, speech and even vision. Most cases of HNSCC require a combination of different treatments such as surgery, chemotherapy (primarily cisplatin based), and radiotherapy. Treatment decisions are largely based on the size of the tumor, the involvement of local lymph nodes, and distant spread. Treatment resistance and local recurrence are significant problems and to date no form of clinical treatment sensitivity prediction is available. A majority of HNSCC tumors overexpresses the epidermal growth factor receptor (EGFR). This receptor is involved in proliferation and DNA repair and is the target of a monoclonal antibody named cetuximab that selectively binds and inhibits EGFR. It is the only targeted therapy available to HNSCC patients and reserved for late stage patients in Sweden. Numerous investigators have searched for predictive markers and we hypothesized that since HNSCC is a very heterogeneous disease a single factor would not be able to predict the treatment outcome. In paper I we explore a panel of predictive factors using a point system, called the number of negative points (NNP), in which we could combine both proteins and genetic variations in an attempt to find a set of markers that could predict the intrinsic cisplatin sensitivity (ICS). The expression level of EGFR, Hsp70, Bax, Bcl-XL, survivin, and COX-2 was determined in 39 HNSCC cell lines. Moreover, the p53, MDM2, FGFR4, XPC, XPD, XRCC1, and XRCC3 genes were analyzed for the presence of specific single nucleotide polymorphisms (SNPs). Pearson’s correlation tests showed that EGFR was the only protein that alone correlated to ICS (r=0.388, P=0.015). The strongest correlation to ICS was found when combining SNPs in XRCC3 and XPD with the expression of EGFR, Hsp70, Bax, and Bcl-2 using the NNP system (r=0.614 P≤0.001). In paper II we assess the intrinsic radiosensitivity (IR), the ICS, and the intrinsic cetuximab sensitivity (ICmabS) as well as their combinations in 25 HNSCC cell lines established from HNSCC biopsies taken at the Department of Otorhinolaryngology and Head and Neck Surgery at Linköping University Hospital. Furthermore we investigate the EGFR status (consisting of EGFR gene copy number, EGFR mRNA, EGFR protein, pEGFR), pAkt and mRNA levels of the seven known EGFR ligands. No correlation was found between the different treatment sensitivities. Cetuximab treatment response was significantly correlated to epiregulin (EREG) mRNA expression (r=-0.408, P=0.043). Cetuximab resistant cell lines tended to have low levels of pEGFR (P=0.13) while resistant cell lines had a significantly lower expression of EGFR pro...

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Expression of Protein Tyrosine Kinases in Head and Neck Squamous Cell Carcinomas

Cited by 101 publications

References 17 publications

Down-regulation of MMP-2 expression due to inhibition of receptor tyrosine kinases by imatinib and carboplatin in HNSCC

Down-regulation of MMP-2 expression due to inhibition of receptor tyrosine kinases by imatinib and carboplatin in HNSCC

Bioprocess Evaluation of Water Soaking-Based Microbiological Biodegradation with Exposure of Cellulosic Microfibers Relevant to Bioconversion Efficiency

Understanding the Role of EGFR in the Treatment of Head and Neck Squamous Cell Carcinoma

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