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Breast Cancer Research and Treatment
Erschienen in: Breast Cancer Research and Treatment 3/2021

22.02.2021 | Preclinical study

Anti-progranulin/GP88 antibody AG01 inhibits triple negative breast cancer cell proliferation and migration

verfasst von: Rupa Guha, Binbin Yue, Jianping Dong, Aditi Banerjee, Ginette Serrero

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2021

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Abstract

Background

Triple negative breast cancer (TNBC) is characterized by invasiveness and short survival. Identifying novel TNBC-targeted therapies, to potentiate standard of care (SOC) therapy, is an unmet need. Progranulin (PGRN/GP88) is a biological driver of tumorigenesis, survival, and drug resistance in several cancers including breast cancer (BC). PGRN/GP88 tissue expression is an independent prognostic factor of recurrence while elevated serum PGRN/GP88 level is associated with poor outcomes. Since PGRN/GP88 expression is elevated in 30% TNBC, we investigated the involvement of progranulin on TNBC.

Methods

The effect of inhibiting PGRN/GP88 expression in TNBC cells by siRNA was investigated. The effects of a neutralizing anti-human PGRN/GP88 monoclonal antibody AG01 on the proliferation and migration of two TNBC cell lines expressing PGRN/GP88 were then examined in vitro and in vivo.

Results

Inhibition of GP88 expression by siRNA and AG01 treatment to block PGRN/GP88 action reduced proliferation and migration in a dose-dependent fashion in MDA-MB-231 and HS578-T cells. Western blot analysis showed decreased expression of phosphorylated protein kinases p-Src, p-AKT, and p-ERK upon AG01 treatment, as well as inhibition of tumor growth and Ki67 expression in vivo.

Conclusion

PGRN/GP88 represents a therapeutic target with companion diagnostics. Blocking PGRN/GP88 with antibody treatment may provide novel-targeted solutions in TNBC treatment which could eventually address the issue of toxicity and unresponsiveness associated with SOC.
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Metadaten
Titel
Anti-progranulin/GP88 antibody AG01 inhibits triple negative breast cancer cell proliferation and migration
verfasst von
Rupa Guha
Binbin Yue
Jianping Dong
Aditi Banerjee
Ginette Serrero
Publikationsdatum
22.02.2021
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2021
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-021-06120-y

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