Kexin Li, Xun Sun, Hudie Li, et al. Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes[J]. Genes & Diseases, 2023,10(4). DOI: 10.1016/j.gendis.2022.08.007.
Suppression of osteosarcoma progression by engineered lymphocyte-derived proteomes
摘要
Abstract
Cancer cells tend to develop resistance to chemotherapy and enhance aggressiveness. A counterintuitive approach is to tame aggressiveness by an agent that acts opposite to chemotherapeutic agents. Based on this strategy
induced tumor-suppressing cells (iTSCs) have been generated from tumor cells and mesenchymal stem cells. Here
we examined the possibility of generating iTSCs from lymphocytes by activating PKA signaling for suppressing the progression of osteosarcoma (OS). While lymphocyte-derived CM did not present anti-tumor capabilities
the activation of PKA converted them into iTSCs. Inhibiting PKA conversely generated tumor-promotive secretomes. In a mouse model
PKA-activated CM suppressed tumor-induced bone destruction. Proteomics analysis revealed that moesin (MSN) and calreticulin (Calr)
which are highly expressed intracellular proteins in many cancers
were enriched in PKA-activated CM
and they acted as extracellular tumor suppressors through CD44
CD47
and CD91. The study presented a unique option for cancer treatment by generating iTSCs that secret tumor-suppressive proteins such as MSN and Calr. We envision that identifying these tumor suppressors and predicting their binding partners such as CD44
which is an FDA-approved oncogenic target to be inhibited
may contribute to developing targeted protein therapy.
The generation and use of animal models of osteosarcoma in cancer research
Integrative transcriptome analysis identifies MYBL2 as a poor prognosis marker for osteosarcoma and a pan-cancer marker of immune infiltration
Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma
Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression
Chondroitin Polymerizing Factor (CHPF) promotes cell proliferation and tumor growth in human osteosarcoma by inhibiting SKP2's ubiquitination while activating the AKT pathway
相关作者
Zhicai Zhang
Jianxiang Liu
Xin Huang
Yizhong Peng
Fengxia Chen
Deyao Shi
Haoyu Guo
Feifei Pu
相关机构
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University
Department of Orthopedics, Wuhan Hospital of Traditional Chinese and Western Medicine (Wuhan No.1 Hospital), Tongji Medical College, Huazhong University of Science and Technology
Hubei Cancer Clinical Study Center, Zhongnan Hospital, Wuhan University
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital