Related Experiment Video
Updated: Jul 24, 2025
08:52
Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells
Published on: June 13, 2018
8.9K
Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes
Kexin Li1,2, Xun Sun1,2, Hudie Li1,2
1Department of Pharmacology, School of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China.
Genes & Diseases
|July 3, 2023
Summary
Researchers converted lymphocytes into induced tumor-suppressing cells (iTSCs) by activating protein kinase A (PKA) signaling. PKA-activated iTSCs secrete proteins like moesin and calreticulin, suppressing osteosarcoma progression and bone destruction.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Cancer cells develop chemoresistance and aggressiveness.
- A novel strategy involves using agents that counteract cancer aggressiveness.
- Induced tumor-suppressing cells (iTSCs) have been generated from various cell types.
Purpose of the Study:
- To investigate generating iTSCs from lymphocytes via protein kinase A (PKA) signaling activation.
- To assess the potential of these iTSCs in suppressing osteosarcoma (OS) progression.
- To identify the molecular mechanisms underlying iTSC-mediated tumor suppression.
Main Methods:
- Lymphocytes were cultured and treated to activate or inhibit PKA signaling.
- Conditioned media (CM) from treated lymphocytes were analyzed for anti-tumor capabilities.
- Osteosarcoma progression and bone destruction were evaluated in a mouse model.
- Proteomics analysis identified key proteins in PKA-activated CM.
Main Results:
- PKA activation converted lymphocytes into iTSCs, producing tumor-suppressive CM.
- PKA inhibition generated tumor-promotive secretomes.
- PKA-activated CM significantly suppressed osteosarcoma progression and tumor-induced bone destruction in vivo.
- Moesin (MSN) and calreticulin (Calr) were enriched in PKA-activated CM and acted as extracellular tumor suppressors via CD44, CD47, and CD91.
Conclusions:
- Lymphocytes can be reprogrammed into iTSCs by activating PKA signaling.
- PKA-activated iTSCs offer a novel therapeutic approach for osteosarcoma by secreting tumor-suppressive proteins.
- Identifying these secreted tumor suppressors and their binding partners could lead to targeted protein therapies for cancer.
