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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
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Rat prostate tumors induce DNA synthesis in remote organs
Sofia Halin Bergström1, Marie Lundholm2, Annika Nordstrand2
1Department of Medical Biosciences, Pathology, Umeå University, Building 6M, second floor, 901 87, Umeå, Sweden. sofia.halin@umu.se.
Scientific Reports
|May 13, 2022
Summary
Small, aggressive prostate cancers can alter DNA synthesis in distant organs. This study reveals early systemic effects, suggesting potential for diagnosing aggressive tumors by examining remote tissue changes.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Advanced cancers trigger systemic responses, but early changes from small, aggressive tumors are not well understood.
- Prostate cancer progression and metastasis involve complex systemic interactions.
Purpose of the Study:
- To investigate how localized prostate cancers of varying sizes and metastatic potential influence DNA synthesis in the prostate and remote organs.
- To identify early systemic biomarkers for aggressive prostate cancer.
Main Methods:
- Inoculation of immunocompetent rats with non-metastatic (G) or metastatic (MLL) Dunning prostate tumor cells.
- Daily Bromodeoxyuridine (BrdU) injections to label cells undergoing DNA synthesis.
- Analysis of BrdU labeling, DNA damage (γH2AX), and macrophage infiltration (CD68) in various tissues.
Main Results:
- Both G and MLL tumors increased BrdU labeling in the prostate, lymph nodes, and liver compared to controls.
- MLL tumors, even before metastasis, elevated BrdU labeling in bone marrow and lungs.
- MLL tumor growth correlated with increased BrdU labeling in prostate, lungs, adipose tissue, and muscles, alongside DNA damage and macrophage accumulation in lungs.
Conclusions:
- Small, localized prostate cancers induce DNA synthesis changes in remote tissues in a tumor-type and size-dependent manner.
- These findings suggest that early systemic effects of aggressive prostate cancer could be detectable in other tissues, potentially aiding early diagnosis.
