Relationship between CD44(high)/CD133(high)/CD117(high) cancer stem cells phenotype and Cetuximab and Paclitaxel treatment response in head and neck cancer cell lines

Autor(es)

Silva Galbiatti-Dias, Ana Livia ^[1] ; Mendonca Fernandes, Glaucia Maria ^[1] ; Urbanin Castanhole-Nunes, Marcia Maria ^[1] ; Hidalgo, Luiza Fernandes ^[2] ; Viesi Nascimento Filho, Carlos Henrique ^[1] ; Kawasaki-Oyama, Rosa Sayoko ^[1] ; Muniz Ferreira, Leticia Antunes ^[1] ; Biselli-Chicote, Patricia Mattos ^[1] ; Pavarino, Erika Cristina ^[1] ; Goloni-Bertollo, Eny Maria ^[1]

Afiliação do(s) autor(es)

^[1] FAMERP Sao Jose do Rio Preto Med Sch, Genet & Mol Biol Res Unit UPGEM, Sao Jose Do Rio Preto, SP - Brazil

^[2] FAMERP Sao Jose do Rio Preto Med Sch, Sao Jose Do Rio Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF CANCER RESEARCH; v. 8, n. 8, p. 1633-1641, 2018.
• Citações Web of Science: 4

Resumo

Recent evidence suggests that cancer stem cells (CSCs), a small population of cancer cells that are highly tumourigenic, capable of self-renewal and have the ability to differentiate into cells that constitute the tumor, are the ``drivers{''} of local recurrence and metastatic spread and may be associated with resistant to conventional therapy. The objectives of the study are to identify and characterize two head and neck cancer cell lines with regard CD44(high)/ CD133(high)/CD117(high) profile (CSCs) and CD44(low)/CD133(low)/CD117(low) profile (Non-CSCs); to investigate the influence of chemotherapy treatment in CSCs and compare with Non-CSCs; to evaluate CD44 and EGFR gene expression in CSCs. Fluorescent-activated cell sorting (FACS) using specific cell surface marker combination (CD44, CD117 and CD133) was performed to isolate CSCs of Non-CSCs from cell lines. The Wound Healing assay was performed to confirm the presence of CSCs. After, the CSCs subpopulation and Non-CSCs were cultured and exposed for 24 h to Cetuximab and Paclitaxel treatment, separately. Cell proliferation was determined by MTS assay. CD44 and EGFR gene expression was quantified by quantitative real time PCR (qPCR) using TaqMan (R) Assay in both subpopulations. CSCs subpopulation untreated were considered as relative expression control. We firstly characterized CSCs in HN13 and HEP-2 cell lines with CD44, CD133 and CD117 biomarkers. We treated CSCs and Non-CSCs subpopulations with Cetuximab and Paclitaxel treatment and found that CSCs subpopulations demonstrated more resistance to Paclitaxel chemoterapy, when compared with Non-CSCs subpopulations of oral cancer cell line. These CSCs subpopulations presented up-regulation of CD44 gene and down-regulation of EGFR gene in oral cancer cell line, and down-regulation of CD44 gene and up-regulation of EGFR gene in laryngeal cancer cell line when compared with Non-CSCs subpopulations. We conclude that the combination of CD44, CD133 and CD117 biomarkers have stem cell properties in both cell lines. CSCs has ability to resist to Paclitaxel treatment in oral cancer cell line. CSCs present high expression of CD44 gene and down expression of EGFR gene in oral cancer cell line. CSCs in laryngeal cell line present down expression of CD44 gene and high expression of EGFR gene when compared with cells without characteristics of cancer stem cells. (AU)

• Processo FAPESP: 15/04403-8 - Avaliação de biomarcadores da angiogênese no desenvolvimento do câncer e resposta ao tratamento.
• Beneficiário: Eny Maria Goloni Bertollo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/15009-6 - Identificação de células tronco tumorais em câncer de cabeça e pescoço: expressão gênica e proteica na resposta a quimioterapia
• Beneficiário: Ana Lívia Silva Galbiatti-Dias
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado