General Information
- Project ID
- OEP002689
- Project Name
- SCUBE2 mediates bone metastasis of luminal breast cancer by modulating immune-suppressive osteoblastic niches
- Description
- Estrogen receptor (ER)-positive luminal breast cancer is a subtype with generally lower risk of metastasis to most distant organs. However, bone recurrence occurs preferentially in luminal cancer. The mechanisms of the subtype-specific organotropism remain elusive. Here we show that an ER-regulated secretory protein SCUBE2 contributes to bone tropism of luminal breast cancer. Single-cell RNA sequencing analysis reveals osteoblastic enrichment by SCUBE2 in early bone-metastatic niches. SCUBE2 facilitates release of tumor membrane-anchored SHH to activate Hedgehog signaling in mesenchymal stem cells, thus promoting osteoblast differentiation. Osteoblasts deposit collagens to suppress NK cells via the inhibitory LAIR1 signaling and promote tumor colonization. SCUBE2 expression and secretion are associated with osteoblast differentiation and bone metastasis in human tumors. Targeting Hedgehog by Sonidegib and targeting SCUBE2 with a neutralizing antibody both effectively suppress bone metastasis in multiple metastasis models. Overall, our findings provides an explanation for bone preference in luminal breast cancer and new approaches for metastasis treatment.
- Publications
-
SCUBE2 mediates bone metastasis of luminal breast cancer by modulating immune-suppressive osteoblastic niches
Wu Q, Tian P, He D, et al. SCUBE2 mediates bone metastasis of luminal breast cancer by modulating immune-suppressive osteoblastic niches. Cell Res. 2023;33(6):464-478. doi:10.1038/s41422-023-00810-6
(PMID: 37142671) (DOI: 10.1038/s41422-023-00810-6)
Project information
- Experiments
- 1
Experiment ID Experiment name Experiment type Create Date OEX014477 EP1 Transcriptomic 2021-09-07 - Samples
- 4
Sample ID Sample Name Sample Subject Type Organism Tissue Create Date OES114356 MSC Animalia Mus musculus mesenchymal stem cell 2021-09-07 OES114358 OB-MCF7-CTRL Animalia Mus musculus mesenchymal stem cell 2021-09-07 OES114359 OB-MCF7-SCUBE2-KD1 Animalia Mus musculus mesenchymal stem cell 2021-09-07 OES114360 OB-MCF7-SCUBE2-KD2 Animalia Mus musculus mesenchymal stem cell 2021-09-07 - Runs
- 4
Author Information
- Create Date
- 2021-09-07
- Last Modified
- 2023-03-15
- Submission
- Guohong Hu
- Shanghai Institute of Nutrition and Health,Chinese Academy of Sciences