Host JDP2 expression in the bone marrow contributes to metastatic spread.

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.