The effect of mast cells on the biological characteristics of prostate cancer cells

Ma, Zhiyong; Liang, Yue; Xu, Zhaoliang; Zhang, Sheng; Ma, Yanxue; Li, Zhuoping; Li, Wei; Wang, Dongwen

doi:10.5114/ceji.2018.74867

Cited by 10 publications

(7 citation statements)

References 23 publications

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“…All the treatment groups were predicted to have decreased activated mast cell levels. Mast cells can encourage the progression of PCa by promoting epithelial to mesenchymal transition (EMT) ( Ma et al, 2018 ). Suppression of mast cells by IL-27/cabo can potentially inhibit metastatic tumor growth.…”

Section: Resultsmentioning

confidence: 99%

Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer

Kumar,

Mulia,

Figueiredo

2023

Front. Mol. Biosci.

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Introduction: Prostate cancer is the second leading cause of cancer-related death among American men. Prostate tumor cells exhibit significant tropism for the bone and once metastasis occurs, survival rates fall significantly. Current treatment options are not curative and focus on symptom management. Immunotherapies are rapidly emerging as a possible therapeutic option for a variety of cancers including prostate cancer, however, variable patient response remains a concern. Chemotherapies, like cabozantinib, can have immune-priming effects which sensitize tumors to immunotherapies. Additionally, lower doses of chemotherapy can be used in this context which can reduce patient side effects. We hypothesized that a combination of chemotherapy (cabozantinib) and immunotherapy [Interleukin-27 (IL-27)] could be used to treat bone-metastatic prostate cancer and exert pro-osteogenic effects. IL-27 is a multi-functional cytokine, which promotes immune cell recruitment to tumors, while also promoting bone repair.Methods: To test this hypothesis, in vivo experiments were performed where syngeneic C57BL/6J mice were implanted intratibially with TRAMP-C2ras-Luc cells that are able to form tumors in bone. Immunotherapy was administered in the form of intramuscular gene therapy, delivering plasmid DNA encoding a reporter gene (Lucia), and/or a therapeutic gene (IL-27). Sonoporation was used to aid gene delivery. Following immunotherapy, the animals received either cabozantinib or a vehicle control by oral gavage. Bioluminescence imaging was used to monitor tumor size over time.Results: Combinatorial therapy inhibited tumor growth and improved survival. Further, RNA sequencing was used to investigate the mechanisms involved. Microcomputed tomography and differentiation assays indicated that the combination therapy improved bone quality by enhancing osteoblast differentiation and inhibiting osteoclast differentiation.Discussion: Our conclusion is that a chemo-immunotherapy approach such as the one examined in this work has potential to emerge as a novel therapeutic strategy for treating bone-metastatic prostate cancer. This approach will enable a significant reduction in chemotherapy-associated toxicity, enhance sensitivity to immunotherapy, and improve bone quality.

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Section: Resultsmentioning

confidence: 99%

Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer

Kumar,

Mulia,

Figueiredo

2023

Front. Mol. Biosci.

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“…Prostatic in ammation is related to the development and progression of prostate cancer 41 . The HFD induces stromal in ltrates of in ammatory cells such as macrophages, T cells, monocytes, and mast cells in the prostate 42,43 . Studies…”

Section: Discussionmentioning

confidence: 99%

Physical Exercise Mitigates the Disturbs Caused in Ventral Prostate by High Fat Diet, Clarifying the Role of PPAR-Alpha

Tavares

Veras

Baptista

et al. 2021

Preprint

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Body fat resulting from the consumption of fatty foods develops inflammation, a precursor to obesity, diabetes mellitus and prostatic diseases, causing tissue changes. On the other hand, aerobic physical exercise in conjunction with PPARα promotes an increase in energy expenditure, modulating cellular metabolism by altering prostate cell metabolism. This study aimed to elucidate the effect of the gene transcription factor PPARα as a prostatic regulator associated with the effects of aerobic physical exercise in mice fed to a high-fat diet. Wild Type and PPARα -/- mice (C57BL/6J) were fed a high-fat diet and submitted to aerobic physical training for 8 weeks. Prostates of male mice were analyzed histologically and metabolically for PIN progression. These findings suggest that the absence of PPARα reduces adiposity and but does not modify the expression AR and GR, up-regulate prostate inflammation, and suppresses Fas (CD95/Apo-1) increase in TNF-α, induced by prostatic lesions. On the other hand, aerobic physical exercise was effective in protecting prostatic damage induced by a high-fat diet, both in wild type and in PPARα-/- animals. The absence PPARα induces an inflammatory process and prostatic changes and associated with a high-fat diet, however, these inflammatory processes induce increased apoptosis and may further inhibit cell growth associated with physical exercise.

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“…• MC density and distribution in prostate cancer tissues are linked to diverse prognostic implications, with high mast cell numbers inversely associated with cancer recurrence in certain studies. [82,83] Leukemia • Detected pronounced hyperplasia of MCs and eosinophils in NSG-SGM3 mouse models implanted with CD34 + hematopoietic stem cells or leukemia xenografts.…”

Section: Gastric Tumormentioning

confidence: 99%

The regulatory role and mechanism of mast cells in tumor microenvironment

Ligan

2024

Am J Cancer Res

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Mast cells (MCs) have emerged as pivotal contributors to both the defensive immune response and immunomodulation. They also exhibit regulatory functions in modulating pathological processes across various allergic diseases. The impact of MC presence within tumor tissues has garnered considerable attention, yielding conflicting findings. While some studies propose that MCs within tumor tissues promote tumor initiation and progression, others advocate an opposing perspective. Notably, evidence emphasizes the dual role of MCs in cancer, both as promoters and suppressors, is crucial for optimizing cancer treatment strategies. These conflicting viewpoints have generated substantial controversy, underscoring the need for a comprehensive understanding of MC's role in tumor immune responses.

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The effect of mast cells on the biological characteristics of prostate cancer cells

Cited by 10 publications

References 23 publications

Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer

Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer

Physical Exercise Mitigates the Disturbs Caused in Ventral Prostate by High Fat Diet, Clarifying the Role of PPAR-Alpha

The regulatory role and mechanism of mast cells in tumor microenvironment

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The effect of mast cells on the biological characteristics of prostate cancer cells

Cited by 10 publications

References 23 publications

Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer

Cabozantinib and IL-27 combinatorial therapy for bone-metastatic prostate cancer

Physical Exercise Mitigates the Disturbs Caused in Ventral Prostate by High Fat Diet, Clarifying the Role of&nbsp;PPAR-Alpha

The regulatory role and mechanism of mast cells in tumor microenvironment

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Physical Exercise Mitigates the Disturbs Caused in Ventral Prostate by High Fat Diet, Clarifying the Role of PPAR-Alpha