Acid-sensing receptor GPR4 plays a crucial role in lymphatic cancer metastasis
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View abstract on PubMed
Summary
This summary is machine-generated.The acidic tumor microenvironment promotes lymphatic cancer metastasis by activating lymphatic endothelial cells via G protein-coupled receptor 4 (GPR4). Targeting GPR4 or VCAM-1 may offer new cancer prevention strategies.
Area Of Science
- Oncology
- Cell Biology
- Molecular Biology
Background
- Cancer tissues create an acidic microenvironment due to proton and lactic acid accumulation.
- This acidic environment is implicated in cancer progression and metastasis.
Purpose Of The Study
- To investigate the role of the acidic microenvironment in lymphatic cancer metastasis.
- To identify molecular mechanisms by which acidity affects lymphatic endothelial cells.
Main Methods
- Gene expression profiling (microarray) of human dermal lymphatic endothelial cells (HDLECs) under acidic conditions.
- Analysis of inflammation-related genes, chemokines, and adhesion molecules.
- Investigated the role of G protein-coupled receptor 4 (GPR4) and vascular cell adhesion molecule 1 (VCAM-1).
- Utilized a mouse melanoma model to assess therapeutic interventions.
Main Results
- Acidic conditions upregulated inflammation-related genes, including chemokines (CX3CL1, CXCL6) and VCAM-1, in HDLECs.
- CX3CL1 and CXCL6 promoted HDLEC growth and tube formation.
- VCAM-1 expression enhanced HDLEC adhesion to melanoma cells.
- GPR4 mediated the acid-induced expression of chemokines and VCAM-1.
- Anti-VCAM-1 antibody or GPR4 antagonist suppressed lymph node metastasis in a mouse model.
Conclusions
- The acidic tumor microenvironment promotes lymphatic metastasis by altering lymphatic endothelial cell function through GPR4.
- GPR4 and its downstream molecules (e.g., VCAM-1) are potential therapeutic targets for preventing cancer metastasis.
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