YKL-39 induces monocytes migration and angiogenesis and inversely correlates with metastasis in patients with breast cancer /I. V. Mitrofanova, L. Tengfei, M. V. Zavyalova [et al.]

Электронный ресурс
Другой Автор
Tengfei, L.
Zavyalova, Marina V.
Litvyakov, Nicolay V.
Buldakov, Mikhail A.
Cherdyntseva, Nadezhda V.
Kzhyshkowska, Julia G.
Mitrofanova, Irina V.
Источник
Annals of oncology 2017 Vol. 28, Supplement 5. P. 580
Аннотация
Background: Human chitinase-like proteins are considered as biomarkers of cancer and chronic inflammation.YKL-39 is a unique member of chitinase-like protein family due to its presence only in humans but not in rodents both on gene and protein levels. However, its biological activity and association with tumor progression remains unknown. Methods: YKL-39 expression and secretion in human monocytes-derived macrophages was measured by RT-PCR and ELISA. Monocyte migration was analyzed in a trans-well system. In vitro tube formation assay was performed using HUVEC cells.112 female patients with nonspecific invasive breast cancer of stage IIA-IIIC (T1-4N0-3M0) were included in the study. Confocal microscopy analysis was used to identify cell type expressing YKL-39 in tumor samples.YKL-39 expression level was measured by RT-PCR in tumor biopsy specimens. Results: Human monocytes-derived macrophages differentiated in the presence of IL4 and TGFbeta, but not IL4 alone, were found to express high levels of YKL-39 mRNA and protein. Purified YKL-39 significantly enhanced the migration of human CD14+monocytes by 1.9 fold (p < 0.01) after 1 h, and 4.9 fold (p < 0.01) after 3 h that was comparable with the effect of MCP-1. In vitro tube formation assays using HUVEC cells demonstrated that YKL-39 has a strong pro-angiogenic effect. In human samples of breast cancer YKL-39 was found to be expressed in CD68+ macrophages but not in cancer cells or other stromal cell types. In breast cancer biopsy specimens it was found that high YKL-39 gene expression correlated with the significantly reduced frequency of lymphatic and hematogenous metastasis. Furthermore, high level of YKL-39 expression associated with 100% metastatic-free survival rate (p = 0.015). Conclusions: TGFbeta is a key cytokine inducing production of YKL-39 in macrophages. YKL-39 stimulates critical for tumor progression processes: chemotaxis of monocytes and angiogenesis. However high levels of YKL-39 expression in tumor samples are predictive for metastatic-free survival in patients with breast cancer, suggesting that YKL-39 can program monocytes and newly growing vessels to inhibit metastatic spread.
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$a Background: Human chitinase-like proteins are considered as biomarkers of cancer and chronic inflammation.YKL-39 is a unique member of chitinase-like protein family due to its presence only in humans but not in rodents both on gene and protein levels. However, its biological activity and association with tumor progression remains unknown. Methods: YKL-39 expression and secretion in human monocytes-derived macrophages was measured by RT-PCR and ELISA. Monocyte migration was analyzed in a trans-well system. In vitro tube formation assay was performed using HUVEC cells.112 female patients with nonspecific invasive breast cancer of stage IIA-IIIC (T1-4N0-3M0) were included in the study. Confocal microscopy analysis was used to identify cell type expressing YKL-39 in tumor samples.YKL-39 expression level was measured by RT-PCR in tumor biopsy specimens. Results: Human monocytes-derived macrophages differentiated in the presence of IL4 and TGFbeta, but not IL4 alone, were found to express high levels of YKL-39 mRNA and protein. Purified YKL-39 significantly enhanced the migration of human CD14+monocytes by 1.9 fold (p < 0.01) after 1 h, and 4.9 fold (p < 0.01) after 3 h that was comparable with the effect of MCP-1. In vitro tube formation assays using HUVEC cells demonstrated that YKL-39 has a strong pro-angiogenic effect. In human samples of breast cancer YKL-39 was found to be expressed in CD68+ macrophages but not in cancer cells or other stromal cell types. In breast cancer biopsy specimens it was found that high YKL-39 gene expression correlated with the significantly reduced frequency of lymphatic and hematogenous metastasis. Furthermore, high level of YKL-39 expression associated with 100% metastatic-free survival rate (p = 0.015). Conclusions: TGFbeta is a key cytokine inducing production of YKL-39 in macrophages. YKL-39 stimulates critical for tumor progression processes: chemotaxis of monocytes and angiogenesis. However high levels of YKL-39 expression in tumor samples are predictive for metastatic-free survival in patients with breast cancer, suggesting that YKL-39 can program monocytes and newly growing vessels to inhibit metastatic spread.
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Резюме
Background: Human chitinase-like proteins are considered as biomarkers of cancer and chronic inflammation.YKL-39 is a unique member of chitinase-like protein family due to its presence only in humans but not in rodents both on gene and protein levels. However, its biological activity and association with tumor progression remains unknown. Methods: YKL-39 expression and secretion in human monocytes-derived macrophages was measured by RT-PCR and ELISA. Monocyte migration was analyzed in a trans-well system. In vitro tube formation assay was performed using HUVEC cells.112 female patients with nonspecific invasive breast cancer of stage IIA-IIIC (T1-4N0-3M0) were included in the study. Confocal microscopy analysis was used to identify cell type expressing YKL-39 in tumor samples.YKL-39 expression level was measured by RT-PCR in tumor biopsy specimens. Results: Human monocytes-derived macrophages differentiated in the presence of IL4 and TGFbeta, but not IL4 alone, were found to express high levels of YKL-39 mRNA and protein. Purified YKL-39 significantly enhanced the migration of human CD14+monocytes by 1.9 fold (p < 0.01) after 1 h, and 4.9 fold (p < 0.01) after 3 h that was comparable with the effect of MCP-1. In vitro tube formation assays using HUVEC cells demonstrated that YKL-39 has a strong pro-angiogenic effect. In human samples of breast cancer YKL-39 was found to be expressed in CD68+ macrophages but not in cancer cells or other stromal cell types. In breast cancer biopsy specimens it was found that high YKL-39 gene expression correlated with the significantly reduced frequency of lymphatic and hematogenous metastasis. Furthermore, high level of YKL-39 expression associated with 100% metastatic-free survival rate (p = 0.015). Conclusions: TGFbeta is a key cytokine inducing production of YKL-39 in macrophages. YKL-39 stimulates critical for tumor progression processes: chemotaxis of monocytes and angiogenesis. However high levels of YKL-39 expression in tumor samples are predictive for metastatic-free survival in patients with breast cancer, suggesting that YKL-39 can program monocytes and newly growing vessels to inhibit metastatic spread.