Tumor‐driven like macrophages induced by conditioned media from pancreatic ductal adenocarcinoma promote tumor metastasis via secreting IL‐8

Chen, Shaojie; Lian, Guoda; Li, Jiajia; Zhang, Qiubo; Zeng, Linjuan; Yang, Kege; Huang, Chanyan; Li, Yaqing; Chen, Yinting; Huang, Kaihong

doi:10.1002/cam4.1824

Cited by 39 publications

(35 citation statements)

References 40 publications

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“…2e), but the mechanism of TAMs inducing the EMT of pancreatic cancer cells was not elucidated in this study. Recent reports by others suggested that IL-8 [30], CCL20 [31], and the TLR4/IL10 signaling pathway [15] might be associated with EMT-induction in an in vitro culture system, and further investigations will be necessary to uncover the precise mechanism of EMT induction through the interplay between pancreatic cancer and TAMs.…”

Section: Discussionmentioning

confidence: 99%

The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer

Kuwada

Kagawa

Yoshida

et al. 2018

J Exp Clin Cancer Res

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BackgroundThe peritoneum is one of the most frequent metastatic sites in pancreatic cancer patients, and peritoneal dissemination makes this disease refractory due to aggressive progression and chemoresistance. Although the role of the tumor microenvironment in cancer development is recognized, the correlation between the peritoneal environment and refractoriness of peritoneal dissemination remains unclear. The intraperitoneal tumor-microenvironment and its potential role in the progression of peritoneal dissemination and chemo-refractoriness, focusing especially on macrophages, were investigated.Materials and methodsPeritoneal washes were obtained from pancreatic cancer patients, and cellular components were subjected to immunofluorescence assays. The effects of macrophages induced from monocytic THP-1 cells on pancreatic cancer cells were examined in co-culture conditions. The in vivo effects of macrophages on tumor growth and chemo-sensitivity were investigated by subcutaneously or intraperitoneally co-injecting cancer cells with macrophages into mice.ResultsCD204-positive macrophages were present along with cancer cells in the peritoneal washes. In in vitro co-culture, tumor-associated macrophages affected pancreatic cancer cells, induced the epithelial-to-mesenchymal transition (EMT), and made them more resistant to chemotherapeutic agents. M2 macrophages promoted growth of both subcutaneous tumors and peritoneal dissemination in mice. Furthermore, co-inoculation of M2 macrophages conferred chemoresistance in the peritoneal dissemination mouse model, which significantly shortened their survival.ConclusionIntraperitoneal tumor-associated macrophages potentially play an important role in promotion of peritoneal dissemination and chemoresistance of pancreatic cancer via EMT induction.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0981-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer

Kuwada

Kagawa

Yoshida

et al. 2018

J Exp Clin Cancer Res

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“…The expression of CXCL8 in urine specimens and the tumour microenvironment of bladder cancer patients is significantly higher than that of healthy volunteers (Pignot et al, 2009;Sheryka et al, 2003), and the overexpression of CXCL8 is positively correlated with significantly reduced survival of patients overall (Zhang et al, 2014). It has been shown that TAMs in the solid tumour microenvironment can secrete CXCL8 in large amounts, directly contributing to the progression of pancreatic ductal carcinoma, papillary thyroid cancer, colorectal cell carcinoma, and esophageal squamous cell carcinoma (Chen et al, 2018;Fang et al, 2014;Hosono et al, 2017;Lee et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Tumour-associated macrophages mediate the invasion and metastasis of bladder cancer cells through CXCL8

Zhang

Han

et al. 2020

PeerJ

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Tumour-associated macrophages (TAMs) are associated with both the progression and poor prognosis of a variety of solid tumours. This study aimed to investigate and clarify the tumour-promoting role of CXCL8 secreted by TAMs in the urothelial carcinoma microenvironment of the bladder. Immunohistochemistry (n = 55) was used to detect Chemokine (C-X-C motif) ligand 8 (CXCL8), CD163 (a TAM marker), Matrixmetalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and E-cadherin in cancerous and adjacent tissues of bladder cancer patients. TAMs-like PBM (peripheral blood mononuclear)-derived macrophages were developed using in vitro experiments. T24, 5637, and UM-UC-3 were treated with conditioned medium (CM) for the experimental intervention group, without CM for the blank control group, and with CM and an anti-CXCL8 neutralizing antibody for the experimental control group, respectively. The immunohistochemical study showed that the expression of CXCL8 was significantly upregulated as the number of infiltrating TAMs increased in the tumour tissues. A high expression of CXCL8 significantly correlated with an increase in the expression of MMP-9 and VEGF and a decrease in expression of E-cadherin in the microenvironment. This revealed that TAM-derived CXCL8 is highly associated with bladder cancer migration, invasion, and angiogenesis. The concentration of CXCL8 was significantly higher in CM collected from TAM-like PBM-derived macrophages than that from THP-1 cells. In subsequent in vitro experiments, we found that CM derived from TAM-like PBM-derived macrophages can also increase the migration rate, invasiveness, and pro-angiogenic properties of tumour cells. Additionally, the effect of CXCL8 was significantly diminished by the addition of an anti-CXCL8 neutralizing antibody to CM. The infiltration of TAMs in the tumour microenvironment leads to the elevation of CXCL8, which in turn promotes the secretion of MMP-9, VEGF, and E-cadherin by bladder cancer cells. This alters the migration, invasion, and pro-angiogenic capacity of bladder cancer cells and accelerates cancer progression.

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“…Previous studies indicated that tumor-associated macrophages (TAMs) were abundant in the tumor microenvironment (TME) of PDAC (Chen et al 2018 ; Habtezion et al 2016 ; Zhu et al 2017 ). Therefore, TAMs may be a useful therapeutic target against PDAC.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance and therapeutic potential of the immune checkpoint VISTA in pancreatic cancer

Hou

Pan

Fei

et al. 2020

J Cancer Res Clin Oncol

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Objective V-domain Ig suppressor of T cell activation (VISTA) is a novel immune checkpoint protein that belongs to the B7 family. The aim of this study was to investigate the prognostic significance and therapeutic potential of VISTA in patients with pancreatic cancer. Methods Using immunohistochemistry (IHC), we examined the expression of VISTA and demonstrated the associations between the VISTA and overall survival in 223 PDAC patients from 2 different unrelated retrospective cohorts. The multiplex immunofluorescence was performed to illuminate the relationship between VISTA expression and tumor-infiltrating immune cell subclusters of PDAC. We also verified the findings in The Cancer Genome Atlas (TCGA) dataset. The anti-tumor effect of anti-VISTA therapy was studied by the mouse model with liver metastases of PDAC. Results The VISTA protein was highly expressed in 25.6% of tumor cells (TCs), 38.1% of immune cells, and 26.0% of endothelial cells in 223 PDAC tumor tissues. VISTA expression in TCs was significantly associated with prolonged overall survival. Multiplex immunofluorescence analysis revealed that VISTA level was positively correlated with CD68+ macrophages, CD3+ T cells, and CD19+ B cells in PDAC. However, a higher expression level of VISTA was detected in tumor-infiltrating CD68+ macrophages than in CD3+ T and CD19+ B cells. Furthermore, anti-VISTA antibody treatment significantly reduced the number of metastatic nodules in livers of mouse models of PDAC with liver metastases. Conclusion VISTA expressed in TCs is associated with a favorable prognosis in PDAC. Moreover, immunotherapy with anti-VISTA antibodies may potentially be an effective treatment strategy against PDAC.

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Tumor‐driven like macrophages induced by conditioned media from pancreatic ductal adenocarcinoma promote tumor metastasis via secreting IL‐8

Cited by 39 publications

References 40 publications

The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer

The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer

Tumour-associated macrophages mediate the invasion and metastasis of bladder cancer cells through CXCL8

Prognostic significance and therapeutic potential of the immune checkpoint VISTA in pancreatic cancer

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