Scholarlink

Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p> <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月13日

查看全文
  • Ziqian Peng,
  • Kirsty Hodgson,
  • Matthew Fisher,
  • Shenglin Mei,
  • Margarita Orozco-Moreno,
  • Lizhi Cao,
  • Michael Kemp,
  • Wayne Gatlin,
  • Louisa Donald,
  • Libby Blencoe,
  • Feier Zeng,
  • Michelle A. Lawson,
  • Daniel Ungar,
  • David B. Sykes,
  • David J. Elliott,
  • Li Peng,
  • Benjamin Schumann,
  • Richard Beatson,
  • Ning Wang,
  • Jennifer Munkley

摘要

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.