Prostate Cancer-Producing Granulocyte Colony-Stimulating Factor

Matsuoka, Yoh; Arai, Gaku; Okada, Yasuhiko; Aida, Junko

doi:10.1159/000176037

Cited by 6 publications

(6 citation statements)

References 13 publications

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“…Furthermore, our previous findings suggest a strong association between both G-CSF and G-CSFR in colon and gastric cancer metastasis ( 10 ). In agreement with these findings, in human tumors there are various reports of extremely aggressive G-CSF producing tumors in multiple cancer types, such as lung cancer ( 18 , 19 ), cervical cancer ( 20 ), meningioma ( 21 ), melanoma ( 22 ), breast cancer ( 8 ) and prostate cancer ( 23 ), demonstrating the important and modulatory effect of G-CSF in tumor progression and metastasis.…”

Section: Discussionsupporting

confidence: 78%

G-CSF and G-CSFR Modulate CD4 and CD8 T Cell Responses to Promote Colon Tumor Growth and Are Potential Therapeutic Targets

et al. 2020

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Cytokines are known to shape the tumor microenvironment and although progress has been made in understanding their role in carcinogenesis, much remains to learn regarding their role in tumor growth and progression. We have identified granulocyte colony-stimulating factor (G-CSF) as one such cytokine, showing that G-CSF is linked with metastasis in human gastrointestinal tumors and neutralizing G-CSF in a mouse model of colitis-associated cancer is protective. Here, we set out to identify the role of G-CSF and its receptor, G-CSFR, in CD4 + and CD8 + T cell responses in the tumor microenvironment. MC38 colon cancer cells were injected into WT, G-CSFR −/− mice, or Rag2 −/− mice. Flow cytometry, Real Time PCR and Multiplex cytokine array analysis were used for in vitro T cell phenotype analysis. Adoptive transfer of WT or G-CSFR −/− CD4 + of CD8 + T cells were performed. Mouse tumor size, cytokine expression, T cell phenotype, and cytotoxic activity were analyzed. We established that in G-CSFR −/− mice, tumor growth of MC38 colon cancer cells is significantly decreased. T cell phenotype and cytokine production were also altered, as both in vitro and in vivo approaches revealed that the G-CSF/G-CSFR stimulate IL-10-producing, FoxP3-expressing CD4 + and CD8 + T cells, whereas G-CSFR −/− T cells exhibit increased IFNγ and IL-17A production, leading to increased cytotoxic activity in the tumor microenvironment. Furthermore, peritumoral injection of recombinant IFNγ or IL-17A inhibited colon and pancreas tumor growth compared to controls. Taken together, our data reveal an unknown mechanism by which G-CSF, through its receptor G-CSFR, promotes an inhibitory Treg phenotype that limits tumor immune responses and furthermore suggest that targeting this cytokine/receptor axis could represent a novel therapeutic approach for gastrointestinal, and likely other tumors with high expression of these factors.

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Section: Discussionsupporting

confidence: 78%

G-CSF and G-CSFR Modulate CD4 and CD8 T Cell Responses to Promote Colon Tumor Growth and Are Potential Therapeutic Targets

et al. 2020

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“…VEGF represents the prominent angiogenic factor that promotes the proliferation, survival, migration and tube formation of endothelial cells. We then examined, in untreated and EA treated LnCap cells, the levels of VEGF and others growth factors involved in prostate cancer progression such as Fibroblast growth factor (FGF), Granulocyte colony-stimulating factor (G-CSF), Hepatocyte growth factor (HGF) [47,48,49]. Moreover, since chronic inflammation has been suggested to favour prostate cancer development [50], the levels of Interleukin 15 (IL-15) were measured.…”

Section: Resultsmentioning

confidence: 99%

Effects of Ellagic Acid on Angiogenic Factors in Prostate Cancer Cells

Vanella

Giacomo

Acquaviva

et al. 2013

Cancers

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Background: Several natural antioxidants, including ellagic acid (EA), have been reported to have chemotherapeutic activity in vivo and in vitro settings. Cytochrome P450 (CYP) activity and synthesis of both epoxyeicosatrienoic acids (EETs) and 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), together with vascular endothelial growth factor (VEGF) and heme oxygenase system (HO) have emerged as important modulators of tumor growth and metastasis. Methods: The anti-angiogenic effects of EA were investigated in the human prostatic cancer cell line LnCap. HO-1, HO-2, CYP2J2 and soluble epoxyde hydrolase (sEH) expressions were evaluated by western blotting. Levels of VEGF and osteoprotegerin (OPG) were determined in the culture supernatant using an ELISA assay, while CYP mRNAs were determined by qRT-PCR. Results: EA treatment induced a significant decrease (p < 0.05) in HO-1, HO-2 and CYP2J2 expression, and in VEGF and OPG levels. Similarly CYP2J2, CYP4F2 and CYPA22 mRNAs were significantly (p < 0.05) down-regulated by EA treatment. The decrease in CYP2J2 mRNA was associated with an increase in sEH expression. Conclusions: Results reported in the present study highlighted the ability of EA to modulate a new pathway, in addition to anti-proliferative and pro-differentiation properties, via a mechanism that involves a decrease in eicosanoid synthesis and a down-regulation of the HO system in prostate cancer.

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“…G-CSF productions by lung [14] and bladder [15] cancer cells have been reported to be associated with an invasive behavior of these cancer cells. Matsuoka et al reported a case of prostate cancer cells to produce G-SCF by immunohistochemical analyses, indicating its prognostic implications in prostate cancer outcome [16]. …”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines

Liang

Liu

et al. 2012

Tumor Biol.

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Bone marrow metastases are formed in the late phases of prostate cancer disease. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are present in the microenvironment of the bone marrow and play a vital role in cell biology therein. The present study was to investigate the influence of SCF and G-CSF on stem-like properties in prostate cancer cell lines. Upon stimulation with SCF or G-CSF, higher levels of CD117, ABCG2, and CD44 were observed in PC-3 and DU145 cells examined by flow cytometry. Simultaneously, the expressions of Oct3/4 and Nanog were upregulated. Moreover, quantitative real-time PCR verified that the increased Nanog under the stimulations was mostly derived from NANOGP8. In parallel with the increasing expressions of these proteins, higher colony and sphere formation efficiencies were seen in these cells in response to the cytokine stimulations. Furthermore, a synergistic effect of SCF and G-CSF on colony and sphere formations and ABCG2 expression was disclosed. Our results indicate a favorable bone marrow niche for prostate cancer cells where higher levels of cell stemness are maintained at least partly by the cytokines SCF and G-CSF.

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Prostate Cancer-Producing Granulocyte Colony-Stimulating Factor

Cited by 6 publications

References 13 publications

G-CSF and G-CSFR Modulate CD4 and CD8 T Cell Responses to Promote Colon Tumor Growth and Are Potential Therapeutic Targets

G-CSF and G-CSFR Modulate CD4 and CD8 T Cell Responses to Promote Colon Tumor Growth and Are Potential Therapeutic Targets

Effects of Ellagic Acid on Angiogenic Factors in Prostate Cancer Cells

Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines

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