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Contemporaneous Inflammatory, Angiogenic, Fibrogenic, and Angiostatic Cytokine Profiles of the Time-to-Tumor Development by Cancer Cells to Orchestrate Tumor Neovascularization, Progression, and Metastasis

Overview
Journal Cells
Publisher MDPI
Date 2024 Oct 25
PMID 39451257
Authors
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Abstract

Cytokines can promote various cancer processes, such as angiogenesis, epithelial to mesenchymal transition (EMT), invasion, and tumor progression, and maintain cancer stem-cell-like (CSCs) cells. The mechanism(s) that continuously promote(s) tumors to progress in the TME still need(s) to be investigated. The data in the present study analyzed the inflammatory, angiogenic, fibrogenic, and angiostatic cytokine profiles in the host serum during tumor development in a mouse model of human pancreatic cancer. Pancreatic MiaPaCa-2-eGFP cancer cells were subcutaneously implanted in RAG2xCγ double mutant mice. Blood samples were collected before cancer cell implantation and every week until the end point of the study. The extracted serum from the blood of each mouse at different time points during tumor development was analyzed using a Bio-Plex microarray analysis and a Bio-Plex 200 system for proinflammatory (IL-1β, IL-10, IFN-γ, and TNF-α) and angiogenic and fibrogenic (IL-15, IL-18, basic FGF, LIF, M-CSF, MIG, MIP-2, PDGF-BB, and VEGF) cytokines. Here, we find that during cancer cell colonization for tumor development, host angiogenic, fibrogenic, and proinflammatory cytokine profiling in the tumor-bearing mice has been shown to significantly reduce host angiostatic and proinflammatory cytokines that restrain tumor development and increase those for tumor growth. The proinflammatory cytokines IL-15, IL-18, and IL-1β profiles reveal a significant host serum increase after day 35 when the tumor began to progress in growth. In contrast, the angiostatic cytokine profiles of TNFα, MIG, M-CSF, IL-10, and IFNγ in the host serum revealed a dramatic and significant decrease after day 5 post-implantation of cancer cells. OP treatment of tumor-bearing mice on day 35 maintained high levels of angiostatic and fibrogenic cytokines. The data suggest an entirely new regulation by cancer cells for tumor development. The findings identify for the first time how pancreatic cancer cells use host cytokine profiling to orchestrate the initiation of tumor development.

References
1.
Tanikawa T, Wilke C, Kryczek I, Chen G, Kao J, Nunez G . Interleukin-10 ablation promotes tumor development, growth, and metastasis. Cancer Res. 2011; 72(2):420-9. PMC: 3261323. DOI: 10.1158/0008-5472.CAN-10-4627. View

2.
Hrynyk M, Ellis J, Haxho F, Allison S, Steele J, Abdulkhalek S . Therapeutic designed poly (lactic-co-glycolic acid) cylindrical oseltamivir phosphate-loaded implants impede tumor neovascularization, growth and metastasis in mouse model of human pancreatic carcinoma. Drug Des Devel Ther. 2015; 9:4573-86. PMC: 4539083. DOI: 10.2147/DDDT.S90170. View

3.
Albini A, Bruno A, Noonan D, Mortara L . Contribution to Tumor Angiogenesis From Innate Immune Cells Within the Tumor Microenvironment: Implications for Immunotherapy. Front Immunol. 2018; 9:527. PMC: 5895776. DOI: 10.3389/fimmu.2018.00527. View

4.
Keeley E, Mehrad B, Strieter R . CXC chemokines in cancer angiogenesis and metastases. Adv Cancer Res. 2010; 106:91-111. PMC: 3069502. DOI: 10.1016/S0065-230X(10)06003-3. View

5.
Yang Y, Lundqvist A . Immunomodulatory Effects of IL-2 and IL-15; Implications for Cancer Immunotherapy. Cancers (Basel). 2020; 12(12). PMC: 7761238. DOI: 10.3390/cancers12123586. View