Specific Targeting of HER2-Positive Head and Neck Squamous Cell Carcinoma Line HN5 by Idarubicin-ZHER2 Affibody Conjugate

2018 ◽  
Vol 19 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Marzieh Ghanemi ◽  
Aminollah Pourshohod ◽  
Mohammad Ali Ghaffari ◽  
Alireza kheirollah ◽  
Mansour Amin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Line ◽  
Squamous Cell ◽  
Optimum Concentration ◽  
Her2 Positive ◽  
Affibody Molecules ◽  
Specific Targeting ◽  
Mcf 7

Background:Expression of human epidermal growth factor receptor type 2 (HER2) in head and neck squamous cell carcinoma (HNSCC) cell line HN5 can be employed with great opportunities of success for specific targeting of anti-cancer chemotherapeutic agents.Objective:In the current study, HER2-specific affibody molecule, ZHER2:342 (an engineered protein with great affinity for HER2 receptors) was selected for conjugation to idarubicin (an anti-neoplastic antibiotic).Method:ZHER2:342 affibody gene with one added cysteine code at the its 5′ end was synthesized de novo and then inserted into pET302 plasmid and transferred to E. Coli BL21 hosting system. After induction of protein expression, the recombinant ZHER2 affibody molecules were purified using Ni- NTA resin and purity was analyzed through SDS-PAGE. Affinity-purified affibody molecules were conjugated to idarubicin through a heterobifunctional crosslinker, sulfosuccinimidyl 4-(Nmaleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). Specific toxicity of idarubicin-ZHER2 affibody conjugate against two HER2-positive cells, HN5 and MCF-7 was assessed through MTT assay after an exposure time of 48 hours with different concentrations of conjugate.Results:Idarubicin in the non-conjugated form showed potent toxic effects against both cell lines, while HN5 cells were significantly more sensitive compared to MCF-7 cells. Dimeric ZHER2 affibody showed a mild decreasing effect on growth of both HN5 and MCF-7 cells at optimum concentration. Idarubicin-ZHER2 affibody conjugate at an optimum concentration reduced viability of HN5 cell line more efficiently compared to MCF-7 cell line.In conclusion, idarubicin-ZHER2 affibody conjugate in optimum concentrations can be used for specific targeting and killing of HN5 cells.

scholarly journals Radiation Sensitization of Basal Cell and Head and Neck Squamous Cell Carcinoma by the Hedgehog Pathway Inhibitor Vismodegib

2018 ◽  
Vol 19 (9) ◽  
pp. 2485 ◽  
Author(s):  
Stephanie Hehlgans ◽  
Patrick Booms ◽  
Ömer Güllülü ◽  
Robert Sader ◽  
Claus Rödel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Line ◽  
Squamous Cell ◽  
Hedgehog Signaling ◽  
Cell Cycle Distribution ◽  
Hedgehog Signaling Pathway

Vismodegib, an inhibitor of the Hedgehog signaling pathway, is an approved drug for monotherapy in locally advanced or metastatic basal cell carcinoma (BCC). Data on combined modality treatment by vismodegib and radiation therapy, however, are rare. In the present study, we examined the radiation sensitizing effects of vismodegib by analyzing viability, cell cycle distribution, cell death, DNA damage repair and clonogenic survival in three-dimensional cultures of a BCC and a head and neck squamous cell carcinoma (HNSCC) cell line. We found that vismodegib decreases expression of the Hedgehog target genes glioma-associated oncogene homologue (GLI1) and the inhibitor of apoptosis protein (IAP) Survivin in a cell line- and irradiation-dependent manner, most pronounced in squamous cell carcinoma (SCC) cells. Furthermore, vismodegib significantly reduced proliferation in both cell lines, while additional irradiation only slightly further impacted on viability. Analyses of cell cycle distribution and cell death induction indicated a G1 arrest in BCC and a G2 arrest in HNSCC cells and an increased fraction of cells in SubG1 phase following combined treatment. Moreover, a significant rise in the number of phosphorylated histone-2AX/p53-binding protein 1 (γH2AX/53BP1) foci in vismodegib- and radiation-treated cells was associated with a significant radiosensitization of both cell lines. In summary, these findings indicate that inhibition of the Hedgehog signaling pathway may increase cellular radiation response in BCC and HNSCC cells.

Hepatocyte Growth Factor/Scatter Factor Stimulates Mitogenesis and Migration of a Head and Neck Squamous Cell Carcinoma Cell Line

2002 ◽  
Vol 127 (4) ◽  
pp. 271-278 ◽  
Author(s):  
Jeffery Fleigel ◽  
Jack Sedwick ◽  
Lori J. Kornberg
Keyword(s):  
Squamous Cell Carcinoma ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Line ◽  
Squamous Cell ◽  
Cultured Cells ◽  
Scatter Factor ◽  
Hepatocyte Growth

OBJECTIVE: We sought to assess the effect of extracellular matrix and hepatocyte growth factor/scatter factor (HGF/SF) on the growth and motility of cultured squamous cell carcinoma of the head and neck (SCCHN) cells. METHODS: Cultured cells were incubated in the presence of HGF/SF. The effect of HFG/SF on cell growth, motility, and phosphorylation of the signaling proteins FAK and Erk was determined. RESULTS: HGF/SF is both mitogenic and motogenic to the human SCCHN cell line FaDu. Incubation of FaDu cells in the presence of HGF/SF led to a rapid increase in phosphorylation of both FAK and the growth-promoting kinase Erk. HGF/SF-induced phosphorylation of FAK and Erk was observed in both detached and attached SCCHN cells. However, phosphorylation was much greater in attached cells. CONCLUSIONS AND SIGNIFICANCE: The mitogenic and motogenic activities of HGF/SF may contribute to the pathogenesis of SCCHN in vivo.

Personalized Medicine Approach for an Exceptional Response to Multiple-recurrent and Metastatic HER2-positive Oropharyngeal Squamous Cell Carcinoma

2017 ◽  
Vol 126 (4) ◽  
pp. 334-339 ◽  
Author(s):  
Nolan B. Seim ◽  
Stephen Y. Kang ◽  
Milan Bhandari ◽  
Riley G. Jones ◽  
Theodoros N. Teknos
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Chemotherapeutic Agent ◽  
Tumor Biology ◽  
Oropharyngeal Squamous Cell Carcinoma ◽  
Her2 Positive ◽  
Recurrent Squamous Cell Carcinoma ◽  
Unexpected Outcomes

Introduction: Advanced stage squamous cell carcinoma of the head and neck carries an overall poor prognosis, and survivorship gains have remained relatively stagnant compared to other malignancies due to its complex tumor biology and lack of proven effective targeting agents. Methods: We present a case of an exceptional responder to molecular-targeted therapy for metastatic oropharyngeal squamous cell carcinoma using a chemotherapeutic agent FDA approved for breast cancer and targeting the HER2/Neu receptor in order to discuss the larger clinical implications. Results: The National Cancer Institute (NCI) has recently instituted the Exceptional Responders Initiative in order to identify such patients with unexpected outcomes in order to expedite the development of additional targeted therapies. This case illustrates the opportunity for cure using targeted oncogene identification in a scenario of recurrent squamous cell carcinoma with lung metastasis typically considered fatal. Conclusions: Molecular tumor analysis is an infrequently utilized tool in head and neck squamous cell carcinoma; however, as understanding of biologic mechanisms improves, additional molecular targets will become available and expand treatment opportunities such as HER2/Neu targeting. The Exceptional Responders Initiative is a unique strategy with potential to expedite progress.

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