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O-Acetyl-GD2 as a Therapeutic Target for Breast Cancer Stem Cells
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O-Acetyl-GD2 as a Therapeutic Target for Breast Cancer Stem Cells
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Journal Article
O-Acetyl-GD2 as a Therapeutic Target for Breast Cancer Stem Cells
2022
Overview
A sugar-lipid molecule called OAcGD2 is a novel marker for breast cancer stem cells. Treatment with anti-OAcGD2 mAb8B6 may have superior anticancer efficacy by targeting cancer stem cells, thereby reducing metastasis and recurrence of cancer.
Cancer stem cells (CSCs) that drive tumor progression and disease recurrence are rare subsets of tumor cells. CSCs are relatively resistant to conventional chemotherapy and radiotherapy. Eradication of CSCs is thus essential to achieve durable responses. GD2 was reported to be a CSC marker in human triple-negative breast cancer, and anti-GD2 immunotherapy showed reduced tumor growth in cell lines. Using a specific anti-OAcGD2 antibody, mAb8D6, we set out to determine whether OAcGD2
cells exhibit stem cell properties and mAb8D6 can inhibit tumor growth by targeting OAcGD2
CSCs.
OAcGD2 expression in patient-derived xenografts (PDXs) of breast cancer was determined by flow cytometric analyses using mAb8D6. The stemness of OAcGD2
cells isolated by sorting and the effects of mAb8B6 were assessed by CSC growth and mammosphere formation
and tumor growth
using PDX models.
We found that the OAcGD2 expression levels in six PDXs of various molecular subtypes of breast cancer highly correlated with their previously defined CSC markers in these PDXs. The sorted OAcGD2
cells displayed a greater capacity for mammosphere formation
and tumor initiation
than OAcGD2
cells. In addition, the majority of OAcGD2
cells were aldehyde dehydrogenase (ALDH
) or CD44
CD24
, the known CSC markers in breast cancer. Treatment of PDXs-bearing mice with mAb8B6, but not doxorubicin, suppressed the tumor growth, along with reduced CSCs as assessed by CSC markers and
tumorigenicity.
, mAb8B6 suppressed proliferation and mammosphere formation and induced apoptosis of OAcGD2
breast cancer cells harvested from PDXs, in a dose-dependent manner. Finally, administration of mAb8B6
dramatically suppressed tumor growth of OAcGD2
breast CSCs (BCSCs) with complete tumor abrogation in 3/6 mice.
OAcGD2 is a novel marker for CSC in various subtypes of breast cancer. Anti-OAcGD2 mAb8B6 directly eradicated OAcGD2
cells and reduced tumor growth in PDX model. Our data demonstrate the potential of mAb8B6 as a promising immunotherapeutic agent to target BCSCs.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Animals
/ Antibodies, Monoclonal - pharmacology
/ antibody
/ breast cancer stem cells markers
/ Breast Neoplasms - pathology
/ Cell Proliferation - drug effects
/ Female
/ glycosphingolipid (GSL) glycans
/ Humans
/ Mice
/ Neoplastic Stem Cells - drug effects
/ Neoplastic Stem Cells - pathology
/ PDX (patient-derived xenografts)
/ Tumors
