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Updated: Mar 31, 2026
A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies
Published on: March 8, 2014
Host JDP2 expression in the bone marrow contributes to metastatic spread
Yelena Barbarov1, Michael Timaner1, Dror Alishekevitz1
1Department of Cell Biology and Cancer Science, the B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Abstract:
The c-Jun Dimerization Protein 2, JDP2, is a basic leucine zipper protein member of the activator protein-1 (AP-1) family of transcription factors. JDP2 typically suppresses gene transcription through multiple mechanisms and plays a dual role in multiple cellular processes, including cell differentiation and proliferation which is dependent on AP-1 function. Whereas the role of JDP2 expression within cancer cells has been studied, its role in stromal cells at the tumor microenvironment is largely unknown. Here we show that mice lacking JDP2 (JDP2-/-) display a reduced rate of metastasis in Lewis lung carcinoma (LLC) and polyoma middle T-antigen (PyMT) breast carcinoma mouse models. The replacement of wild-type bone marrow derived cells (BMDCs) with JDP2-deficient BMDCs recapitulates the metastatic phenotype of JDP2-/- tumor-bearing mice. In vitro, conditioned medium of wild-type BMDCs significantly potentiates the migration and invasion capacity of LLC cells as compared to that of JDP2-/- BMDCs. Furthermore, wild-type BMDCs secrete CCL5, a chemokine known to contribute to metastasis, to a greater extent than JDP2-/- BMDCs. The supplementation of CCL5 in JDP2-/- BMDC conditioned medium was sufficient to potentiate the invasion capacity of LLC. Overall, this study suggests that JDP2-expressing BMDCs within the tumor microenvironment contribute to metastatic spread.
Insights
The transcription factor JDP2 in bone marrow cells promotes cancer metastasis. Lacking JDP2 reduces tumor spread, indicating its role in the tumor microenvironment.
Area of Science:
- Molecular Biology
- Cancer Research
- Immunology
Background:
- The transcription factor JDP2 (c-Jun Dimerization Protein 2) is part of the AP-1 family.
- JDP2 typically suppresses gene transcription and influences cell differentiation and proliferation.
- The function of JDP2 in cancer cells is known, but its role in stromal cells of the tumor microenvironment is unclear.
Purpose of the Study:
- To investigate the role of JDP2 in stromal cells, specifically bone marrow-derived cells (BMDCs), in cancer metastasis.
- To determine if JDP2 deficiency in BMDCs affects tumor metastasis in mouse models.
Main Methods:
- Utilized JDP2-deficient (JDP2-/-) mice and Lewis lung carcinoma (LLC) and polyoma middle T-antigen (PyMT) breast carcinoma models.
- Performed bone marrow chimeric experiments by replacing wild-type BMDCs with JDP2-deficient BMDCs.
- Analyzed conditioned medium from wild-type and JDP2-/- BMDCs for their effects on LLC cell migration and invasion in vitro.
- Quantified the secretion of CCL5 chemokine by BMDCs.
Main Results:
- Mice lacking JDP2 exhibited reduced metastasis in LLC and PyMT models.
- Replacing wild-type BMDCs with JDP2-deficient BMDCs in tumor-bearing mice mimicked the reduced metastatic phenotype.
- Conditioned medium from wild-type BMDCs enhanced LLC cell migration and invasion compared to medium from JDP2-/- BMDCs.
- Wild-type BMDCs secreted higher levels of the chemokine CCL5 than JDP2-/- BMDCs, and CCL5 supplementation restored LLC cell invasion.
Conclusions:
- JDP2 expression in bone marrow-derived cells within the tumor microenvironment promotes cancer metastasis.
- JDP2-expressing BMDCs contribute to tumor spread, partly through the secretion of CCL5.
- Targeting JDP2 in stromal cells could be a potential therapeutic strategy to inhibit cancer metastasis.
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