CD147-high extracellular vesicles promote gastric cancer metastasis via VEGF/AKT/eNOS and AKT/mTOR pathways

  • 0Institute of Pathology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

|

|

Summary

This summary is machine-generated.

Gastric cancer cell-derived extracellular vesicles (EVs) carrying high levels of CD147 promote tumor metastasis by disrupting endothelial barrier integrity. CD147-high EVs serve as potential biomarkers and therapeutic targets for gastric cancer.

Area Of Science

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background

  • Extracellular vesicles (EVs) mediate intercellular communication and are implicated in cancer metastasis.
  • Gastric cancer cell-derived EVs are known to enhance tumor spread by increasing endothelial barrier permeability.
  • The specific molecular drivers and mechanisms of EV-mediated gastric cancer metastasis remain incompletely understood.

Purpose Of The Study

  • To identify key effector molecules within gastric cancer EVs responsible for promoting tumor metastasis.
  • To elucidate the molecular mechanisms by which these EVs compromise endothelial barrier integrity.
  • To evaluate the diagnostic and prognostic potential of identified EV markers in gastric cancer.

Main Methods

  • Characterization of molecules expressed on gastric cancer cell-derived EVs.
  • In vitro assays to assess the impact of CD147-high EVs on endothelial cell function and barrier integrity.
  • Analysis of key signaling pathways (VEGF/AKT/eNOS/NO, AKT/mTOR/p70S6K) activated by CD147-high EVs.
  • Correlation analysis of CD147 expression in patient tissues and plasma EVs with clinical outcomes.

Main Results

  • CD147 was identified as a key molecule highly expressed on gastric cancer-derived EVs.
  • CD147-high EVs significantly promoted endothelial dysfunction, increased vascular permeability, and enhanced tumor cell migration.
  • Activation of VEGF/AKT/eNOS/NO and AKT/mTOR/p70S6K pathways by CD147-high EVs led to cytoskeletal reorganization and VE-cadherin internalization.
  • High CD147 expression in tissues and plasma EVs correlated with advanced tumor stage, poor prognosis, and reduced survival.

Conclusions

  • CD147-high EVs are critical mediators of gastric cancer metastasis by disrupting endothelial barrier function.
  • CD147 is a potential diagnostic and prognostic biomarker for gastric cancer.
  • Targeting CD147-high EVs presents a promising therapeutic strategy for gastric cancer treatment.

Related Concept Videos

mTOR Signaling and Cancer Progression 03:03

3.9K

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

Mitogens and the Cell Cycle 02:38

7.0K

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...

Cancer Cell Migration through Invadopodia 01:35

2.4K

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...

Metastasis 02:30

5.7K

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...

The Tumor Microenvironment 02:17

6.8K

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

Regulation of Angiogenesis and Blood Supply 01:24

2.7K

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...