Related Experiment Video
Updated: Jun 16, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
CXCR4/SDF1 mediate hypoxia induced chondrosarcoma cell invasion through ERK signaling and increased MMP1 expression
Xiaojuan Sun1, Lei Wei, Qian Chen
1Department of Orthopaedics, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI, USA.
Background:
Chondrosarcoma is a disease that does not respond to conventional cytotoxic chemotherapy and expression of MMP1 is a marker for a poor prognosis. The mechanism of increased MMP1 expression in chondrosarcoma is not completely known. Our goal is to identify molecular pathways that could serve as therapeutic targets. Chondrosarcoma become hypoxic as they grow, are capable of eliciting an angiogenic response, and typically metastasize to the lungs. The present study determined the effect of hypoxia and specifically HIF-1a on expression of CXCR4 and MMP1 and their role in chondrosarcoma cell invasion.
Results:
CXCR4 and its ligand, SDF1, are upregulated in primary chondrosarcoma tumors compared to normal articular cartilage, and CXCR4 was upregulated in chondrosarcoma cell line JJ compared to normal chondrocytes. Hypoxia and specifically HIF-1a increased CXCR4 and MMP1 expression in JJ cell line and chondrosarcoma invasion in vitro. The hypoxia mediated increase in MMP1 expression and chondrosarcoma invasion could be inhibited by siRNA directed at HIF-1a or CXCR4, the CXCR4 inhibitor AMD3100, as well as with ERK inhibitor U0126 and ERK siRNA.
Conclusions:
Chondrosarcoma cell invasion is increased by hypoxia induced expression of CXCR4 and MMP1 and is mediated by HIF-1a and ERK. Both invasion and MMP1 can be inhibited with CXCR4 blockade, suggesting that CXCR4/SDF1 signaling may be a therapeutic target for chondrosarcoma.
Insights
Hypoxia increases chondrosarcoma invasion by upregulating CXCR4 and MMP1 via HIF-1a. Blocking CXCR4 inhibits invasion and MMP1, suggesting it as a therapeutic target for chondrosarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chondrosarcoma is resistant to chemotherapy, with MMP1 expression indicating poor prognosis.
- Tumor hypoxia and HIF-1a signaling are implicated in chondrosarcoma progression and metastasis.
- Understanding molecular pathways is crucial for identifying novel therapeutic targets.
Purpose of the Study:
- To investigate the role of hypoxia and HIF-1a in regulating CXCR4 and MMP1 expression in chondrosarcoma.
- To determine the impact of these factors on chondrosarcoma cell invasion.
- To identify potential therapeutic targets for chondrosarcoma treatment.
Main Methods:
- Analysis of CXCR4 and MMP1 expression in chondrosarcoma tumors and cell lines.
- In vitro studies exposing chondrosarcoma cells to hypoxia.
- Manipulation of HIF-1a, CXCR4, and ERK pathways using siRNA and inhibitors (AMD3100, U0126).
Main Results:
- CXCR4 and MMP1 were upregulated in chondrosarcoma tumors and cells.
- Hypoxia and HIF-1a significantly increased CXCR4, MMP1 expression, and chondrosarcoma invasion.
- Inhibition of HIF-1a, CXCR4, or ERK pathways reduced MMP1 expression and invasion.
Conclusions:
- Hypoxia-induced CXCR4 and MMP1 expression, mediated by HIF-1a and ERK, enhances chondrosarcoma invasion.
- CXCR4 blockade effectively inhibits both invasion and MMP1 expression.
- CXCR4/SDF1 signaling represents a promising therapeutic target for chondrosarcoma.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:35Cancer Cell Migration through Invadopodia
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...