Keywords

1. Interleukin-7 Prostate Cancer
2. Prostate Cancer Treatment
3. JAK Inhibitor Prostate Cancer
4. IL-7 Blocking Antibody
5. Epithelial-Mesenchymal Transition Prostate Cancer

In a pivotal study published in Scientific Reports, researchers at the Seoul National University College of Medicine and affiliates have made significant headway in unraveling the complexity of prostate cancer cell invasiveness and identifying potential therapeutic targets. The seminal paper, “Interleukin-7 Contributes to the Invasiveness of Prostate Cancer Cells by Promoting Epithelial-Mesenchymal Transition,” is a testament to years of meticulous research and could lead to breakthroughs in prostate cancer treatment protocols.

DOI: 10.1038/s41598-019-43294-4

Researchers have long been intrigued by the precise mechanisms by which interleukin-7 (IL-7), a cytokine involved in T cell development, drives the invasive behavior of prostate cancer cells. While the beneficial roles of IL-7 in immune function are widely acknowledged, its darker facet in promoting cancer invasiveness remains a complex puzzle. The research led by Seol Min A, Kim Jin-Hee, Oh Keunhee, and Kim Gwanghun presents compelling evidence pointing to IL-7 as a key player in facilitating tumor progression and metastasis in prostate cancer.

The study employed metastatic prostate cancer PC-3 cell line derivatives to investigate IL-7’s role in tumor invasiveness. Intriguingly, IL-7 was found to stimulate migration and invasion of PC-3 cells, along with an upsurge in the phosphorylation of signal transducer and activator of transcription 5, Akt, and extracellular signal-regulated kinase – key players in cellular signaling pathways. Counteracting these effects, a Janus kinase (JAK) inhibitor and an IL-7-blocking antibody significantly diminished PC-3 cell invasiveness, showcasing their potential as therapeutic tools.

More so, the researchers observed that IL-7 boosts tumor sphere formation and raises the expression of epithelial-mesenchymal transition (EMT) markers. This realization is of immense importance as EMT is a biological process that allows epithelial cells to acquire mesenchymal properties – including increased motility and invasiveness, laying the groundwork for metastasis.

A crucial part of the study involved a murine model where the lentiviral delivery of IL-7Rα to PC-3 cells markedly augmented bone metastasis compared to control groups. Further compelling evidence emerged from the gene expression profiling of human prostate cancer cells sourced from The Cancer Genome Atlas. The profile revealed a strong association between EMT pathways and prostate cancers that highly express both IL-7 and IL-7Rα.

The implications of these findings carry weight far beyond the scientific community. Prostate cancer is a leading malignancy among male populations, with its propensity to metastasize to the bone wreaking havoc and significantly impacting both quality of life and survival rates. Despite advancements in diagnostic screenings and treatment protocols, the prognosis for metastatic prostate cancer remains guarded. In light of this, the revelation of IL-7’s role in cancer invasiveness and the effectiveness of IL-7-targeting strategies in reducing metastasis propose a beacon of hope.

The authors reference several key studies to contextualize their results, including those exploring the pathways of IL-7 and MMP activation in cancer. These studies have laid the foundation for comprehending IL-7’s nuanced roles in inflammation and immunity, its influence on matrices like Matrigel, and its expression across different cancers.

Consequently, based on these findings, the deployment of JAK inhibitors and IL-7 blocking antibodies could usher in a new era in prostate cancer therapeutics. Medications like tofacitinib have exhibited marked effectiveness in autoimmune conditions by targeting analogous pathways, thus presenting a viable therapeutic blueprint.

Moreover, the study emphasizes the multifaceted role of enzyme matrix metalloproteinases (MMPs) in cancer metastasis. MMPs are implicated in the breakdown of extracellular matrix components, which facilitates cancer cell invasion and dissemination. Therefore, the modulation of MMP activity by components like IL-7 adds another layer to the understanding and management of cancer progression.

The repository of data from The Cancer Genome Atlas and the experimental results from this study suggest that the sinister partnership of IL-7 with its receptor and the downstream activation of EMT pathways are prime targets for therapeutic intervention. This could herald a shift in treatment paradigms towards a more targeted, personalized medicine approach.

To further highlight the translational impact of this research, the study not only informs about the insidious role of IL-7 in driving prostate cancer metastasis but also provides the groundwork for the future development of strategies to impede or reverse the process. This exciting development underscores the potential of targeted immunotherapies to more effectively combat prostate cancer.

In conclusion, the article published in Scientific Reports is a momentous stride forward in the fight against prostate cancer. The insights into IL-7-mediated invasiveness of prostate cancer cells shed light on a critical aspect of tumor biology, paving the way for novel therapeutic strategies that aim directly at the heart of cancer aggressiveness.

References

1. 10.1038/s41598-019-43294-4
2. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67:7–30. doi: 10.3322/caac.21387. PMID: 28055103
3. Tharmalingam S, Chow E, Harris K, Hird A, Sinclair E. Quality of life measurement in bone metastases: A literature review. J Pain Res. 2008;1:49–58. PMC3004617 PMID: 21197288
4. Saad F, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst. 2004;96:879–882. doi: 10.1093/jnci/djh141. PMID: 15173273
5. Schluns KS, Kieper WC, Jameson SC, Lefrancois L. Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat Immunol. 2000;1:426–432. doi: 10.1038/80868. PMID: 11062503
6. Qu H, et al. IL-7/IL-7 receptor axis stimulates prostate cancer cell invasion and migration via AKT/NF-kappaB pathway. Int Immunopharmacol. 2016;40:203–210. doi: 10.1016/j.intimp.2016.08.017. PMID: 27611862
7. Park SL, Lee EJ, Kim WJ, Moon SK. p27KIP1 is involved in ERK1/2-mediated MMP-9 expression via the activation of NF-kappaB binding in the IL-7-induced migration and invasion of 5637 cells. Int J Oncol. 2014;44:1349–1356. doi: 10.3892/ijo.2014.2290. PMID: 24504262