Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy

Litviakov, N. V.; Цыганов, М. М.; Larionova, Irina; Ибрагимова, М. К.; Deryusheva, Irina V; Kazantseva, Polina; Slonimskaya, Е. М.; Фролова, И. Г.; Чойнзонов, Е. Л.; Чердынцева, Н. В.; Kzhyshkowska, Julia

doi:10.1007/s00280-018-3594-8

Cited by 34 publications

(31 citation statements)

References 44 publications

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“…We found that high gene expression of YKL-39, in biopsies obtained before NAC, positively correlated with increased risk of distant metastasis and poor response (stabilization or progressive disease) to therapy (17) ( Table 7). In our other study that included 68 female patients with BC (Russian cohort) who received anthracycline-containing NAC, the absence of clinical response is associated with the presence of M2+ macrophage phenotype (YKL-39-CCL18+ or YKL-39+CCL18−) (20). In our study of patients who underwent neoadjuvant chemotherapy (multiple schemes) CD68+ TAMs in areas with parenchymal elements negatively correlated with lymphatic metastasis (52).…”

Section: Tams and Breast Cancer Treatmentmentioning

confidence: 68%

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Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

et al. 2020

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Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth

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Section: Tams and Breast Cancer Treatmentmentioning

confidence: 68%

“…In addition to scavenging function (10,11,13), stabilin-1 acts as an intracellular sorting receptor that targets chitinase-like proteins SI-CLP and YKL-39 to the secretory pathway (14)(15)(16)(17)(18)(19). SI-CLP and YKL-39, in turn, regulate monocyte recruitment and angiogenesis (15,17,18,20).…”

Section: Introductionmentioning

confidence: 99%

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

et al. 2020

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“…12 CCL18, a member of the CC chemokine family, is mainly secreted by M2-type TAMs. 7,8 Excessive secretion of CCL18 has been observed in multiple human malignancies, including breast carcinoma, [9][10][11]13 hepatocellular carcinoma, 14 ovarian cancer, 15,16 nasopharyngeal carcinoma, 17 lung cancer, [18][19][20] colon cancer 21,22 and pancreatic ductal adenocarcinoma. 23,24 Expression of CCL18 is associated with tumour initiation and progression, and therefore, could be used to predict the prognosis of patients with breast cancer.…”

Section: Backg Rou N Dmentioning

confidence: 99%

CCL18 promotes the metastasis of squamous cell carcinoma of the head and neck through MTDH‐NF‐κB signalling pathway

Qin

Wang

Zhu

et al. 2019

J Cellular Molecular Medi

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Metastasis is one of the primary causes for high mortality in patients with squamous cell carcinoma of the head and neck (SCCHN). Our previous study showed that chemokine (C‐C motif) ligand 18 (CCL18), derived from tumour‐associated macrophages (TAMs), regulates SCCHN metastasis by promoting epithelial‐mesenchymal transition (EMT) and preserving stemness. However, the underlying mechanism needs to be further investigation. Interestingly, metadherin (MTDH) expression was induced when SCCHN cells were stimulated with recombinant CCL18 protein in this study. Suppressing MTDH expression reversed CCL18‐induced migration, invasion and EMT in SCCHN cells. Furthermore, the NF‐κB signalling pathway was involved in the MTDH knock‐down cells with CCL18 stimulation. We performed ELISA to evaluate the CCL18 levels in the serums of 132 treatment‐naive SCCHN patients, 25 patients with precancerous lesion and 32 healthy donors. Our results demonstrated that serum CCL18 levels were significantly higher in SCCHN patients than patients with precancerous lesion and healthy individuals. CCL18 levels were found to be significantly correlated with tumour classification, clinical stage, lymph node metastasis and histological grade in SCCHN patients. Thus, our findings suggest that CCL18 may serve as a potential biomarker for diagnosis of SCCHN and promote SCCHN invasion, migration and EMT by MTDH‐NF‐κB signalling pathway.

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“…Tumor-associated macrophage is an essential factor affecting the efficiency of chemotherapy. Among the breast cancer patients with TOP2A overexpression, the absence of clinical response to anthracycline-containing neoadjuvant chemotherapy is associated with the presence of M2+ macrophage phenotype ( Litviakov et al, 2018 ). In addition, TOP2A expression level was significantly negatively correlated with the numbers of macrophages in gastric cancer tissues ( Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Construction and analysis of macrophage infiltration related circRNA-miRNA-mRNA regulatory networks in hepatocellular carcinoma

Chen

Zheng

et al. 2020

PeerJ

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Background Macrophage play a crucial role in regulating tumor progression. This study intended to investigate the circular RNA (circRNA) regulatory network associated with macrophage infiltration in hepatocellular carcinoma (HCC). Methods The immune cell fractions of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium were calculated by Estimation of the Proportion of Immune and Cancer cells algorithm. The differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs) and circRNAs (DEcircRNAs) were identified from HCC and adjacent non-tumor cases of TCGA or Gene Expression Omnibus database. The DEmRNAs related to macrophage were selected by weighted gene co-expression network analysis and then utilized to generate the circRNA-miRNA-mRNA network. A hub circRNA regulatory network was established based on the co-expressed DEmiRNAs and DEmRNAs owning contrary correlation with the clinical characteristics, survival and macrophage infiltration level. A gene signature based on the DEmRNAs in hub network was also generated for further evaluation. The circRNA binding bite for miRNA was detected by luciferase assay. Results High macrophage fraction predicted good survival for HCC. A circRNA-miRNA-mRNA network was constructed by 27 macrophage related DEmRNAs, 21 DEmiRNAs, and 15 DEcircRNAs. Among this network, the expression of hsa-miR-139-5p was negatively correlated with CDCA8, KPNA2, PRC1 or TOP2A. Hsa-miR-139-5p low or targeted DEmRNA high expression was associated with low macrophage infiltration, high grade, advanced stage and poor prognosis of HCC. Additionally, the risk score generated by 4-DEmRNA signature could reflect the macrophage infiltration status and function as an independent prognostic factor for HCC. Finally, hsa_circ_0007456 acting on hsa-miR-139-5p related network was viewed as the hub circRNA regulatory network. Taken together, some circRNA regulatory networks may be associated with macrophage infiltration, which provides clues for mechanism study and therapeutic strategies of HCC.

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Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy

Abstract: Thus, we showed that in patients with breast cancer who received anthracycline-containing NAC the absence of clinical response is associated with the presence of M2+ macrophage phenotype (YKL-39-CCL18 + or YKL-39 + CCL18-) based on TOP2a overexpression data.

Cited by 34 publications

References 44 publications

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

CCL18 promotes the metastasis of squamous cell carcinoma of the head and neck through MTDH‐NF‐κB signalling pathway

Construction and analysis of macrophage infiltration related circRNA-miRNA-mRNA regulatory networks in hepatocellular carcinoma

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