Targeting Siglec-engaging immunosuppressive sialoglycans to suppress prostate cancer bone metastasis

Sep 22, 2026

Prostate cancer causes substantial mortality in men over 50, yet patients with bone metastasis lack curative options. This study quantifies tumour sialoglycans and profiles Siglec receptors across prostate cancer tissues representing clinical heterogeneity. Siglec-3 (CD33), Siglec-7, and Siglec-9 engaging sialoglycans are upregulated in bone metastatic disease, with Siglec-7 and -9 ligands linked to worse prognosis. Engineered sialidase E-612 suppresses tumour growth, enhances immune cell infiltration, and prolongs survival in syngeneic mouse models, supporting Siglec–sialoglycan targeting as clinically actionable.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Background

Methods

Results

Conclusions

Introduction

[www.nature.com/bjc](www.nature.com/bjc British)[ British](www.nature.com/bjc British) Journal of Cancer ARTICLE OPEN Translational Therapeutics Targeting Siglec-engaging immunosuppressive sialoglycans to suppress prostate cancer bone metastasis Ziqian Peng1, Kirsty Hodgson 1, Matthew Fisher2, Shenglin Mei3,4, Margarita Orozco-Moreno 1, Lizhi Cao5, Michael Kemp5, Wayne Gatlin5, Louisa Donald 1, Libby Blencoe 1, Feier Zeng6, Michelle A. Lawson 2, Daniel Ungar7, David B. Sykes8, David J. Elliott1, Li Peng5, Benjamin Schumann9,10,11, Richard Beatson 12, Ning Wang2,6 and Jennifer Munkley 1 ✉ © The Author(s) 2026 | | BACKGROUND: Prostate cancer is a leading cause of male cancer-related deaths over the age of 50 . New treatment options are urgently needed, especially for prostate tumours that have spread to bone. Targeting aberrant sialylation holds substantial potential for the development of new therapeutics but is relatively unexplored in the context of prostate cancer.
METHODS: Here, using high-afﬁnity Siglec-based sialoglycan-binding reagents (HYDRA) for immunohistochemistry, we quantify tumour sialoglycans in tissues representing the full clinical heterogeneity of prostate cancer. Using immunoﬂuorescence, we proﬁle Siglec receptors in prostate tumours, and using syngeneic mouse models, we evaluate an engineered dual-action sialidase (E-612) as a treatment for prostate cancer bone metastasis.
RESULTS: We ﬁnd that sialoglycans that can engage Siglec-3 (CD33), Siglec-7 and Siglec-9 are upregulated in bone metastatic prostate cancer and show that sialoglycan ligands for Siglec-7 and -9 correlate with poorer patient prognosis. Furthermore, we reveal Siglec receptors and Siglec ligands are co-expressed by immune cells in prostate-derived tumours growing in bone. Indicating the Siglec-sialoglycan axis is clinically actionable in prostate cancer, we show systemic therapy with E-612 can suppress the growth of tumours, increase immune cell inﬁltration and prolong survival times of mice with bone metastasis. CONCLUSIONS: Our ﬁndings identify a novel mechanism involving Siglec-engaging sialoglycans in driving the growth of prostate cancer bone metastasis and demonstrate that targeting this axis using an engineered sialidase can impede lethal prostate cancer | | | --- | --- | --- | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | progression. | | | | | British Journal of Cancer (2026) 135:1164–1177; [https://doi.org/10.1038/s41416-026-03544-5](https://doi.org/10.1038/s41416-026-03544-5) | | | | | | INTRODUCTION Prostate cancer is a common cancer in men leading to more than 350,000 deaths worldwide every year [1] . When prostate cancer is localised, curative therapies are available and the 5-year survival rate is 97%, but for patients with metastasis, 5-year survival can beas low as 32%[2] . The growth of prostate tumours is driven by androgen receptor (AR) signalling, and initial therapeutic options for advanced prostate cancer are hormone-based therapies such as anti-androgens [3–5] . However, eventually most tumours will become resistant to hormone therapy and progress to lethal castrate resistant prostate cancer (CRPC) [6] . Bone metastasis is common in prostate cancer, with up to 80% of patients with advanced disease diagnosed with tumours that have spread to the skeleton [2] . Although it is possible to manage the symptoms [7], no curative treatments are available for prostate cancer that has spread to bone and there is a critical need to develop new therapeutic options. An area of innovation in the search for new cancer therapies is the targeting of cancer-associated glycosylation [8, 9] . Glycans decorate all cells and most secreted proteins and play essential roles in all biological processes [10] . Cancer cells have a different‘glycan coat’ than healthy cells [11, 12], and this aberrant glycosylation

FAQs

Why are new therapies urgently needed for prostate cancer bone metastasis?

Bone metastasis is common and current care can manage symptoms but lacks curative treatments. Patients with metastatic disease have substantially reduced 5-year survival.

Which Siglec-related sialoglycans are linked to bone metastatic prostate cancer?

Sialoglycans that engage Siglec-3 (CD33), Siglec-7, and Siglec-9 are upregulated in bone metastatic prostate cancer, and Siglec-7 and -9 ligands correlate with poorer patient prognosis.

How does the engineered sialidase E-612 affect disease progression in models?

Systemic E-612 therapy suppresses tumour growth, increases immune cell infiltration, and prolongs survival times in mice with bone metastasis.

Sep 22, 2026

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