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Cancer Biomark. 2019;24(1):97-107. doi: 10.3233/CBM-181947.

α2δ1 may be a potential marker for cancer stem cell in laryngeal squamous cell carcinoma.

Huang C1,2,1, Li Y1,1, Zhao W3, Zhang A1, Lu C1, Wang Z1, Liu L1.

Author information

1
Department of Otolaryngology and Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
2
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan, China.
3
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Cell Biology, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Abstract

Cancer stem cells (CSCs) have the ability to dictate tumor initiation, recurrence, and metastasis. Here, we examined the expression of aα2δ1+ in laryngeal cancer tissues and further determined the effect of α2δ1 on the migratory ability and tumorigenicity of laryngeal cancer cells. Immunofluorescence staining revealed that α2δ1 was positive in 13 (13/16, 81.25%) cases in laryngeal squamous cell carcinoma (LSCC) tissues, 7 (7/16, 43.75%) cases in paracancerous tissues and only 2 (2/16, 12.5%) cases in normal tumor tissues. Our quantitative RT-PCR assays further showed that α2δ1+ LSCC cells expressed significantly higher levels of stem cell-associated genes and drug efflux and resistance genes versusα2δ1- cells. Sphere-forming assays demonstrated higher sphere-forming efficiency in the α2δ1+versusα2δ1- subpopulation. Our Matrigel assays showed that α2δ1+ cells exhibited significantly greater invasive and migratory ability than α2δ1- cells. Furthermore, the percentage of purified α2δ1+ in TU686 and TU212 cells treated cisplatin or paclitaxel was significantly higher than that of the control group. Tumor xenograft assays revealed that the tumorigenicity of α2δ1+ cells was much higher than α2δ1- cells. In conclusion, a α2δ1+ subpopulation with CSC-like property was present in laryngeal cancer and possessed high self-renewal activity and was sufficient for tumor growth, differentiation, migration, invasion, and chemotherapeutic resistance. They could represent a promising therapeutic target for LSCC.

KEYWORDS:

Laryngeal squamous cell carcinoma; cancer stem cells; α2δ1

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