Pazopanib-induced changes in protein expression signatures of extracellular vesicles in synovial sarcoma

Kumiko Shiozawa1, Yusuke Yoshioka2, Zhiwei Qiao1

  • 1Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Insights

Secreted proteins in extracellular vesicles from synovial sarcoma cells, particularly Wnt signaling, are altered by pazopanib treatment. This suggests Wnt

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Extracellular vesicles (EVs) mediate intercellular communication through secreted proteins.
  • Synovial sarcoma is a rare soft tissue sarcoma with limited treatment options.
  • Understanding pazopanib response mechanisms is crucial for improving sarcoma treatment.

Purpose of the Study:

  • To investigate the role of proteins secreted by synovial sarcoma cells in pazopanib response.
  • To identify key proteins and signaling pathways involved in pazopanib resistance or sensitivity.

Main Methods:

  • Proteomic analysis of proteins secreted from four synovial sarcoma cell lines (SYO-1, HS-SYII, 1273/99, YaFuSS).
  • Comparison of protein expression in cells, cell-free conditioned media, and extracellular vesicles.
  • Mass spectrometry was used to identify and quantify secreted proteins.
  • Analysis of protein signatures before and after pazopanib treatment.

Main Results:

  • Significantly elevated Wnt protein levels were detected in synovial sarcoma extracellular vesicles.
  • Extracellular vesicle protein profiles exhibited substantial alterations in Wnt signaling pathways following pazopanib treatment.
  • Specific protein signatures in EVs correlated with pazopanib response.

Conclusions:

  • Wnt proteins secreted via extracellular vesicles play a role in the response to pazopanib in synovial sarcoma.
  • EV-derived Wnt signaling is a potential therapeutic target for synovial sarcoma.
  • EV-secreted Wnt proteins may serve as diagnostic biomarkers for sarcoma.

Related Concept Videos

Structural Joints: Synovial Joints01:16

Structural Joints: Synovial Joints

Synovial joints are the most common type of joint in the body. A key structural characteristic for a synovial joint is the presence of a joint cavity. This fluid-filled space is where the articulating surfaces of the bones contact each other. Also, unlike fibrous or cartilaginous joints, the articulating bone surfaces at a synovial joint are not directly connected to each other with fibrous connective tissue or cartilage. This gives the bones of a synovial joint the ability to move smoothly...
6.8K
The Extracellular Matrix01:42

The Extracellular Matrix

Overview
89.0K
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
12.2K
Development of the Limb Synovial Joints01:07

Development of the Limb Synovial Joints

Joints form during embryonic development in conjunction with the formation and growth of the associated bones. The embryonic tissue that gives rise to all bones, cartilage, and connective tissues of the body is called mesenchyme.
The mesenchymal stem cells differentiate into chondrocytes that form the hyaline cartilage, and later the cartilaginous model of the bone. This model further transforms into a bone. This process is known as endochondral ossification.
During development, the limbs...
2.3K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
6.4K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.5K