LGR5 in breast cancer and ductal carcinoma in situ: a diagnostic and prognostic biomarker and a therapeutic target

BMC Cancer
Catharina HagerlingVicki Plaks

Abstract

Novel biomarkers are required to discern between breast tumors that should be targeted for treatment from those that would never become clinically apparent and/or life threatening for patients. Moreover, therapeutics that specifically target breast cancer (BC) cells with tumor-initiating capacity to prevent recurrence are an unmet need. We investigated the clinical importance of LGR5 in BC and ductal carcinoma in situ (DCIS) to explore LGR5 as a biomarker and a therapeutic target. We stained BC (n = 401) and DCIS (n = 119) tissue microarrays with an antibody against LGR5. We examined an LGR5 knockdown ER- cell line that was orthotopically transplanted and used for in vitro colony assays. We also determined the tumor-initiating role of Lgr5 in lineage-tracing experiments. Lastly, we transplanted ER- patient-derived xenografts into mice that were subsequently treated with a LGR5 antibody drug conjugate (anti-LGR5-ADC). LGR5 expression correlated with small tumor size, lower grade, lymph node negativity, and ER-positivity. ER+ patients with LGR5high tumors rarely had recurrence, while high-grade ER- patients with LGR5high expression recurred and died due to BC more often. Intriguingly, all the DCIS patients who later died of BC ha...Continue Reading

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Citations

May 1, 2021·Diagnostics·Hoang Dang Khoa TaChih-Yang Wang
May 9, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Joshua S JolissaintWilliam R Jarnagin
May 9, 2021·Journal for Immunotherapy of Cancer·Soudabeh Rad PourJesper Tegner

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Datasets Mentioned

BETA
EGAS00000000083

Methods Mentioned

BETA
transfection
PCR
xenograft
transgenic

Software Mentioned

SPSS Statistics
Oncomine

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