Dataset Information

CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells.

ABSTRACT: Tumor-associated macrophages (TAMs) are involved in tumor progression and poor prognosis in several malignancies. We previously demonstrated the interaction between high numbers of infiltrating TAMs and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To investigate the significance of TAMs in ESCC, we conducted a cDNA microarray analysis of peripheral blood monocytes (PBMo)-derived macrophages and PBMo-derived macrophages stimulated with conditioned media of TE-series ESCC cell lines (TAM-like PBMo-derived macrophages). C-X-C motif chemokine ligand 8 (CXCL8) was up-regulated in the TAM-like PBMo-derived macrophages. Here we confirmed a high expression level of CXCL8 in TAM-like PBMo-derived macrophages and the expression of CXCR1/2, known as CXCL8 receptors, in TE-series ESCC cell lines. Recombinant human CXCL8 induced the ESCC cell lines' migration and invasion by the phosphorylation of Akt and Erk1/2. In indirect co-cultures, not only signal pathway inhibitors but also neutralizing antibodies against CXCL8, CXCR1 and CXCR2 suppressed these phenotypes induced by TAM-like PBMo-derived macrophages. Immunohistochemical analysis of 70 resected ESCC samples showed that high expression levels of CXCL8 in ESCC tissues were significantly associated with lymph node metastasis and poor prognosis. These results suggest that CXCL8 up-regulated in the microenvironment may contribute to ESCC progression by promoting cancer cells' migration and invasion.

SUBMITTER: Hosono M

PROVIDER: S-EPMC5739702 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells.

Hosono Masayoshi M Koma Yu-Ichiro YI Takase Nobuhisa N Urakawa Naoki N Higashino Nobuhide N Suemune Kazuki K Kodaira Himiko H Nishio Mari M Shigeoka Manabu M Kakeji Yoshihiro Y Yokozaki Hiroshi H

Oncotarget 20171120 62

Tumor-associated macrophages (TAMs) are involved in tumor progression and poor prognosis in several malignancies. We previously demonstrated the interaction between high numbers of infiltrating TAMs and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To investigate the significance of TAMs in ESCC, we conducted a cDNA microarray analysis of peripheral blood monocytes (PBMo)-derived macrophages and PBMo-derived macrophages stimulated with conditioned media of TE-series ESCC cell li ...[more]

PMID: 29285315

Similar Datasets

Project description:Tumor-associated macrophages (TAMs) contribute to the progression and mortality of various malignancies. We reported that high numbers of infiltrating TAMs were significantly associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma (ESCC). In our previous investigation of TAMs' actions in ESCC, we compared gene expression profiles between peripheral blood monocyte (PBMo)-derived macrophages and TAM-like macrophages stimulated with conditioned media of ESCC cell lines. Among the upregulated genes in the TAM-like macrophages, we focused on CC chemokine ligand 3 (CCL3), which was reported to contribute to tumor progression in several malignancies. Herein, we observed that not only TAMs but also ESCC cell lines expressed CCL3. A CCL3 receptor, CC chemokine receptor 5 (CCR5) was expressed in the ESCC cell lines. Treating the ESCC cell lines with recombinant human (rh)CCL3 induced the phosphorylations of Akt and ERK, which were suppressed by CCR5 knockdown. Migration and invasion of ESCC cells were promoted by treatment with rhCCL3 and co-culture with TAMs. TAMs/rhCCL3-promoted cell migration and invasion were suppressed by inhibition of the CCL3-CCR5 axis, PI3K/Akt, and MEK/ERK pathways. Treatment with rhCCL3 upregulated MMP2 and VEGFA expressions in ESCC cell lines. Our immunohistochemical analysis of 68 resected ESCC cases showed that high expression of CCL3 and/or CCR5 in ESCC tissues was associated with poor prognosis. High CCR5 expression was associated with deeper invasion, presence of vascular invasion, higher pathological stage, higher numbers of infiltrating CD204+ TAMs, and higher microvascular density. High expression of both CCL3 and CCR5 was an independent prognostic factor for disease-free survival. These results suggest that CCL3 derived from both TAMs and cancer cells contributes to the progression and poor prognosis of ESCC by promoting cell migration and invasion via the binding of CCR5 and the phosphorylations of Akt and ERK. The CCL3-CCR5 axis could become the target of new therapies against ESCC.

Project description:OBJECTIVE:To investigate serum levels of long non-coding RNA (lncRNA) TUSC7 in patients with esophageal squamous cell carcinoma (ESCC), its association with clinicopathological parameters and its role in promoting tumor metastasis and invasion. METHODS:Serum samples were collected from 60 patients with ESCC admitted between January, 2017 and May, 2019, with 60 age- and gender-matched healthy subjects as the control group. Serum level of TUSC7 in ESCC patients and its expression in 4 ESCC cell lines was detected with RT-qPCR. The association of serum TUSC7 level with the clinicopathological features of the patients was analyzed. KYSE-30 cell models with TUSC7 overexpression or knockdown were established, and the proliferation of the cells was examined with MTT assay and their migration and invasion were assessed using wound healing and Transwell assays. Western blotting was used to detect the cellular expressions of the proteins associated with epithelial-mesenchymal transition (EMT). RESULTS:The patients with ESCC had significantly lower serum TUSC7 level than the healthy control subjects (P < 0.05). The ESCC cell lines also expressed lower levels of TUSC7 than normal cells (P < 0.05). Serum TUSC7 level was negatively correlated with tumor staging, lymph node metastasis and infiltration (P < 0.05) but was not significantly correlated with other clinicopathological parameters in ESCC patients. In the invitro cell experiment, overexpression of TUSC7 in KYSE-30 cells significantly inhibited cell migration and invasion (P < 0.05), enhanced the expression of the EMT marker protein E-cadherin and lowered the expressions of N-cadherin, Vimentin and MMP9 (P < 0.05); knocking down TUSC7 in the cells produced the opposite effects. CONCLUSIONS:The down-regulation of TUSC7 expression in the serum of ESCC patients and in ESCC cell lines is associated with the metastasis of ESCC and promotes tumor cell migration and invasion by promoting EMT, indicating the potential of serum TUSC7 level as a molecular marker for diagnosis, treatment and metastasis monitoring of ESCC.

Project description:Oral tongue squamous cell carcinoma (OTSCC) has a high mortality rate and the incidence is rising worldwide. Despite advances in treatment, the disease lacks specific prognostic markers and treatment modality. The spreading of OTSCC is dependent on the tumor microenvironment and involves tumor-associated macrophages (TAMs). Although the presence of TAMs is associated with poor prognosis in OTSCC, the specific mechanisms underlying this are still unknown. The aim here was to investigate the effect of macrophages (Mfs) on HSC-3 tongue carcinoma cells and NF-kappaB activity. We polarized THP-1 cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type Mfs. We then investigated the effect of Mfs on HSC-3 cell migration and NF-kappaB activity, cytokine production and invasion using several different in vitro migration models, a human 3D tissue invasion model, antibody arrays, confocal microscopy, immunohistochemistry and a mouse invasion model. We found that in co-culture studies all types of Mfs fused with HSC-3 cells, a process which was partially due to efferocytosis. HSC-3 cells induced expression of epidermal growth factor and transforming growth factor-beta in co-cultures with M2 Mfs. Direct cell-cell contact between M2 Mfs and HSC-3 cells induced migration and invasion of HSC-3 cells while M1 Mfs reduced HSC-3 cell invasion. M2 Mfs had an excess of NF-kappaB p50 subunit and a lack of p65 subunits both in the presence and absence of HSC-3 cells, indicating dysregulation and pro-tumorigenic NF-kappaB activation. TAM-like cells were abundantly present in close vicinity to carcinoma cells in OTSCC patient samples. We conclude that M2 Mfs/TAMs have an important role in OTSCC regulating adhesion, migration, invasion and cytokine production of carcinoma cells favouring tumor growth. These results demonstrate that OTSCC patients could benefit from therapies targeting TAMs, polarizing TAM-like M2 Mfs to inflammatory macrophages and modulating NF-kappaB activity.

Project description:BackgroundAccurate prediction of tumor invasion depth in superficial esophageal squamous carcinoma (SESC) is essential for deciding the appropriate treatment strategy. We proposed novel endoscopic criteria to differentiate between mucosal and submucosal esophageal cancers and to evaluate the diagnostic accuracy and usefulness of the criteria.MethodsA total of 352 patients who underwent endoscopic or surgical resection for SESC between 1991 and 2010 were included. First, the novel endoscopic criteria were created based on the endoscopic features of 60 randomly selected patients as follows: for T1m cancers, I. flat or slightly elevated or depressed lesion with smooth/even surface of any size, II. slightly elevated lesion of ≤ 1 cm with granular or uneven surface, III. hyperemic flat lesion of ≤ 3 cm with granular or uneven surface, IV. slightly depressed lesion of ≤ 2 cm with uneven surface and for T1sm cancers, I. irregularly (unevenly) nodular or protruded lesion of any size, II. slightly elevated lesion of > 1 cm with granular or uneven surface, III. hyperemic flat lesion of > 3 cm with granular or uneven surface, IV. irregularly (unevenly) depressed lesion of > 2 cm, and V. ulcerative lesion of any size. Next, the endoscopic findings of the remaining 292 patients were reviewed according to the criteria.ResultsThe accuracy of novel endoscopic criteria was 79.5% (232/292). The sensitivity and specificity of mucosal cancers were 78.4% and 81.0%, respectively, whereas those for submucosal cancers were 81.0% and 78.4%, respectively. The accuracy for mucosal cancers was high (97.3%, 72/74) when the lesions were flat or slightly elevated/depressed with smooth/even surface regardless of size, whereas that for submucosal cancers was high (85.7%, 18/21) when the lesions were irregular/nodular protrusions regardless of size. In multivariate analysis, macroscopic type IIb lesion was identified as an independent factor affecting accuracy (P < 0.05). The difference in recurrence-free survival rates between endoscopically mucosal and submucosal cancers was significant (P = 0.026).ConclusionThe novel endoscopic criteria appear to be accurate and useful in predicting invasion depth in SESC. Our criteria might help not only to decide the treatment strategy between surgery and endoscopic resection but also to predict the outcomes of SESC.

Dataset Information

CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells.

Publications

CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets