Fernandes Glaucia Maria de Mendonça, Serafim Junior Vilson, Galbiatti-Dias Ana Lívia Silva, Ferreira Leticia Antunes Muniz, Castanhole-Nunes Márcia Maria Urbanin, Kawasaki-Oyama Rosa Sayoko, Maniglia José Victor, Pavarino Erika Cristina, Goloni-Bertollo Eny Maria
Molecular Biology Department, Genetics and Molecular Biology Research Unit (UPGEM), Faculdade de Medicina de São José do Rio Preto (FAMERP) São José do Rio Preto, São Paulo, Brazil.
Department of Otolaryngology and Head and Neck Surgery, Faculdade de Medicina de São José do Rio Preto (FAMERP) São José do Rio Preto, São Paulo, Brazil.
Am J Cancer Res. 2022 Sep 15;12(9):4196-4210. eCollection 2022.
(1) Head and neck cancer (HNC) is the sixth most common cancer worldwide and show low survival rates and drug resistance, which can be due to the presence of cancer stem cells (CSCs), a small cell population with metastatic potential, invasion and self-renewal ability. (2) Here, seven tumor cells were sorted as CD44+/CD117+/CD133+ or ALDH+, considered as HNC stem cells (HNCSCs), and as CD44-/CD117-/CD133- or ALDH-, considered non-HNCSCs after both cells sorted criteria was compared to evaluate cell migration, invasion, and colony forming assays. These subpopulations were treated with Cetuximab, Paclitaxel, or a combination of both drugs and evaluated for cell viability. Quantitative PCR and western blot were performed to evaluate EGFR, TRKB, KRAS and HIF-1α gene and protein expression. (3) HNCSCs presented more colonies and appeared to be more sensitive to the drug combination when compared with non-HNCSCs, regardless cells sorted criteria and primary tumor subsite. The EGFR, TRKB, KRAS and HIF-1α genes and proteins were upregulated in CSCs compared with non-HNCSCs, thus explaining the drug resistance. (4) This study contributes to the better development of specific therapeutic protocols based on Cetuximab and Paclitaxel drugs in the treatment of HNC in the presence of CSCs and cell proliferation biomarkers.
(1) 头颈癌（HNC）是全球第六大常见癌症，生存率低且具有耐药性，这可能是由于癌症干细胞（CSC）的存在，癌症干细胞是一小部分具有转移潜能、侵袭能力和自我更新能力的细胞群体。(2) 在这里，将七个肿瘤细胞分选成CD44+/CD117+/CD133+或ALDH+，视为头颈癌干细胞（HNCSC），以及分选成CD44-/CD117-/CD133-或ALDH-，视为非头颈癌干细胞，在比较两种细胞分选标准后评估细胞迁移、侵袭和集落形成试验。用西妥昔单抗、紫杉醇或两种药物的组合处理这些亚群，并评估细胞活力。进行定量PCR和蛋白质印迹以评估EGFR、TRKB、KRAS和HIF-1α基因及蛋白质表达。(3) 与非头颈癌干细胞相比，无论细胞分选标准和原发肿瘤亚部位如何，头颈癌干细胞形成更多集落，并且似乎对药物组合更敏感。与非头颈癌干细胞相比，CSC中的EGFR、TRKB、KRAS和HIF-1α基因及蛋白质上调，从而解释了耐药性。(4) 本研究有助于在存在CSC和细胞增殖生物标志物的情况下，更好地制定基于西妥昔单抗和紫杉醇药物治疗头颈癌的特定治疗方案。
