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Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model
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Interaction between Tumor Cell Surface Receptor RAGE and Proteinase 3 Mediates Prostate Cancer Metastasis to Bone

Mikhail G Kolonin1, Anna Sergeeva2, Daniela I Staquicini3,4

  • 1The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas. Mikhail.G.Kolonin@uth.tmc.edu rpasqual@salud.unm.edu warap@salud.unm.edu.

Cancer Research
|April 22, 2017
PubMed

Insights

Prostate cancer bone metastasis is driven by interactions between RAGE on cancer cells and PR3 in the bone marrow. This RAGE-PR3 binding promotes tumor cell homing to bone, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background:

  • Prostate cancer frequently metastasizes to bone, a process known as bone tropism.
  • The underlying biological mechanisms for this site-specific metastasis are not fully understood.
  • Recent research suggests a role for interactions between RAGE and proteinase 3 (PR3).

Purpose of the Study:

  • To investigate the role of Receptor for Advanced Glycation Endproducts (RAGE) and Proteinase 3 (PR3) interaction in prostate cancer bone metastasis.
  • To elucidate the signaling pathways involved in RAGE-PR3-mediated tumor cell homing.

Main Methods:

  • In vitro binding assays to assess PR3 interaction with RAGE on prostate cancer cells.
  • Analysis of signal transduction pathways, including ERK1/2 and JNK1 phosphorylation.
  • Preclinical experimental metastasis models using human prostate cancer cells with ectopic RAGE expression.

Main Results:

  • PR3 directly binds to RAGE on prostate cancer cells, mediating homing to the bone marrow.
  • RAGE-PR3 interaction activates a nonproteolytic signaling cascade, involving ERK1/2 and JNK1 phosphorylation.
  • Ectopic RAGE expression in prostate cancer cells significantly enhances bone marrow homing in preclinical models.

Conclusions:

  • RAGE-PR3 interactions are a key mechanism driving prostate cancer cell homing to the bone marrow.
  • This interaction plays a critical role in bone metastasis during prostate cancer progression.
  • Targeting RAGE-PR3 interactions may offer novel therapeutic strategies for prostate cancer bone metastasis.

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