Voltage-dependent Calcium Channel α2δ1 Subunit is a Specific Candidate Marker for Identifying Gastric Cancer Stem Cells

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Jun 20

PMID 31213895

Citations 8

Authors

Ziran Zhang

Wei Zhao

Xiaoting Lin

Jing Gao

Zhiqian Zhang

Lin Shen

Affiliations

Soon will be listed here.

Abstract

Cancer stem cells (CSCs) are a subpopulation of cancer cells with self-renewal property and responsible for tumor malignancy, progression and drug resistance. Researches on CSC-specific markers in gastric cancer remain limited. Our current study explored the expression of voltage-dependent calcium channel α2δ1 subunit and the potential of using α2δ1 as a CSC marker in gastric cancer. We also compared the specificity of α2δ1 and CD44 in identifying gastric cancer stem cells (GCSCs). Expression of α2δ1 was analyzed in gastric cancer cell lines, patient-derived xenograft (PDX) models and clinical samples of malignant ascites of gastric cancer patients. α2δ1 gastric cancer cells were isolated from gastric cancer cell lines. CSC properties of α2δ1 gastric cancer cells were then verified by subsequent tests both in vitro and in vivo. The expression level of α2δ1 was found to differ drastically among gastric cancer cell lines, PDX models and clinical samples of malignant ascites. α2δ1 gastric cancer cells sorted from HGC-27 and SGC-7901 cell lines demonstrated significant self-renewal properties, including tumorigenic capacity, sphere-formation capacity and asymmetric differentiation potential. Knockdown of α2δ1 in α2δ1 HGC-27 significantly inhibited CSC properties and rendered HGC-27 more sensitive to chemotherapy. Flow cytometry showed that α2δ1 gastric cancer cells accounted for a small fraction of CD44 gastric cancer cells. Isolated CD44α2δ1 HGC-27 cells displayed more significant tumorigenic capacity and sphere-forming capacity compared with their CD44α2δ1 counterparts. α2δ1 gastric cancer cells possessed CSC properties. α2δ1 could be a proper marker in identifying GCSCs with superior specificity than CD44. The combination of α2δ1 and CD44 could be used to identify GCSCs with improved accuracy. Knockdown of α2δ1 combined with chemotherapy displayed higher therapeutic efficacy on gastric cancer cells, suggesting that α2δ1 could be a potential target for anticancer treatment.

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