Targeting stromal cell Syndecan-2 reduces breast tumour growth, metastasis and limits immune evasion

Area of Science:

• Oncology
• Cell Biology
• Immunology

Background:

• Tumorigenesis is significantly influenced by stromal cells within the tumor microenvironment (TME).
• Syndecan-2 (SDC2) is identified as a key molecule expressed on specific stromal cells in breast cancer tissue.

Purpose of the Study:

• To investigate the role of Syndecan-2 (SDC2) in breast cancer progression and metastasis.
• To evaluate the therapeutic potential of targeting SDC2 in the tumor microenvironment (TME).

Main Methods:

• In vitro analysis of patient-derived tumor-associated stromal cells (TASCs) for SDC2 function.
• In vivo studies using orthotopic immunocompromised and syngeneic breast cancer models to assess SDC2 manipulation.
• Development and testing of a syndecan-2-peptide inhibitor.

Main Results:

• SDC2 expression in TASCs modulates TGFβ signaling, cell migration, and immunosuppression.
• Overexpression of SDC2 in TASCs enhanced tumor growth and metastasis, while SDC2 reduction attenuated these effects.
• The syndecan-2-peptide inhibited TASC migration and immunosuppression, reducing tumor growth and immunosuppression in vivo.

Conclusions:

• Stromal SDC2 plays a critical role in promoting breast cancer growth and metastasis via TGFβ signaling.
• Targeting stromal SDC2 presents a promising therapeutic strategy to inhibit tumor progression and enhance immune control within the TME.