The α2δ1 subunit of the voltage-gated calcium channel acts as a potential candidate for breast cancer tumor initial cells biomarker.

Abstract

BACKGROUND:

The voltage-gated calcium channel subunit alpha 2 delta 1 (α2δ1) is a functional tumor initial cells (TICs) marker for some solid cancer cells. This study aimed to investigate whether α2δ1 can be used as a potential TIC marker for breast cancer cells.

METHODS:

α2δ1+ and α2δ1- cells were identified and sorted from the breast cancer cell lines MDA-MB-231, MDA-MB-435s and ZR-75-1 by Immunofluorescence (IF) and Fluorescent-activated cell sorting (FACS) analyses. Spheroid formation in vitro and tumorigenesis in NOD/SCID mice were assessed to determine the self-renewal and serial transplantation abilities of these cells. Using a lentivirus infection system for α2δ1 in breast cancer cell lines, we determined the mRNA levels of stemnessassociated genes by quality real-time PCR (qRT-PCR). Boyden chamber and wounding assays were further performed to detect the migration of α2δ1 overexpression cells. Bioinformatics explored the relationship of molecular classification of breast cancer and drug resistance.

RESULTS:

α2δ1 presents on the cytomembrane of breast cancer cells, with a positive rate of 1.5-3%. The α2δ1+ cells in breast cancer cell lines have a stronger self-renewal ability and tumor initiating properties in vitro and in vivo. Overexpressing α2δ1 successfully enhanced the sphere-forming efficiency, and upregulated the expression of stemness-associated genes, and increased cell migration. However, seldom significant was available between estrogen receptor +/- (ER+/-), progesterone receptor (PR+/-), and Her2+/-.

CONCLUSIONS:

Breast cancer cells positive for the α2δ1 charactered tumor initiation, and α2δ1 is a potential TIC marker for breast cancer that further promotes the migration.

• Authors: Meng Li, Wenmin Zhang, Xiaodan Yang, Guo An, Wei Zhao
• Journal: Cancer biomarkers : section A of Disease markers (Cancer Biomark) Vol. 31 Issue 3 Pg. 295-305 ( 2021) ISSN: 1875-8592 [Electronic] Netherlands
• PMID: 33896833 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CACNA1S protein, human
• CACNA2D1 protein, human
• Calcium Channels
• Calcium Channels, L-Type

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (metabolism, pathology)
• Calcium Channels (metabolism)
• Calcium Channels, L-Type
• Cell Line, Tumor
• Female
• Humans
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Neoplastic Stem Cells (metabolism, pathology)
• Transfection