Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer

Zhang, Bin; Ye, Huilin; Ren, Xiubao; Zheng, Shusen; Zhou, Quanbo; Chen, Changhao; Q, Lin; Li, Guolin; Wei, Liuya; Fu, Zhiqiang; Zhang, Yuting; Hu, Chonghui; Li, Zhihua; Chen, Rufu

doi:10.1016/j.canlet.2019.06.005

Cited by 53 publications

(35 citation statements)

References 38 publications

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“…In fact, the CD51 + TAM or ZEB1 + TAM subtype mentioned above was an M2-like phenotype [32,33]. Here we identified that Wnt5a + TAM was also a phenotype of M2-like TAM.…”

Section: Discussionsupporting

confidence: 52%

“…Therefore, we thought that TAM subtype would be a better indicator for predicting tumor prognosis. Zhang et al reported that high CD51 + TAM subtype infiltration was significantly correlated with poor clinical outcomes in pancreatic cancer [32]. Cortes and colleagues showed that ZEB1 + TAMs were associated with tumor growth, poor prognosis, and chemotherapy resistance in ovarian carcinoma [33].…”

Section: Discussionmentioning

confidence: 99%

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Wnt5a/CaMKII/ERK/CCL2 axis is required for tumor-associated macrophages to promote colorectal cancer progression

et al. 2020

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Tumor-associated macrophages (TAMs) are closely correlated with tumor occurrence, invasion, and metastasis. However, factors affecting the biological functions of TAMs in colorectal cancer (CRC) are incompletely understood. Here, we found that Wnt5a was mainly expressed on TAMs of tumor stroma but not on CRC cells. Subsequently, we found that Wnt5a + TAMs facilitated tumor cell proliferation and migration, and recruited macrophages infiltration. Furthermore, Wnt5a knockdown impaired the pro-tumor roles of TAMs in vivo and in vitro. Mechanistically, the cancer-promoting roles of Wnt5a in TAMs depended on CaMKII-ERK pathway-mediated CCL2 secretion. Our data reveal the crucial role played by TAM-expressed Wnt5a in CRC tumorigenesis through paracrine secretion of CCL2. We first report the connection between Wnt5a/CaMKII/ERK/CCL2 axis and biological functions of TAMs in tumor microenvironment, indicating that Wnt5a may be a novel therapeutic target for CRC.

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“…In fact, the CD51 + TAM or ZEB1 + TAM subtype mentioned above was an M2-like phenotype [32,33]. Here we identified that Wnt5a + TAM was also a phenotype of M2-like TAM.…”

Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Wnt5a/CaMKII/ERK/CCL2 axis is required for tumor-associated macrophages to promote colorectal cancer progression

et al. 2020

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“…As discussed above, recent advances in the role of EMT and PCSCs in tumor progression, metastasis, chemo-resistance, and the mechanisms integrated with aberrant biochemical signals and the underlying pathways have been surveyed in this review. Furthermore, WNT signaling cascades cross-interaction with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49) [40,[153][154][155][156][157][158] . Aberrant canonical and non-canonical WNT signaling in human malignancies, including PDAC are involved in CSC survival, bulk-tumor expansion and invasion/metastasis [158] .…”

Section: Relevance Of Pcscs In Pdac Developmentmentioning

confidence: 99%

Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance

Safa

2020

JCMT

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Metastasis, tumor progression, and chemoresistance are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). Tumor dissemination is associated with the activation of an epithelial-tomesenchymal transition (EMT) process, a program by which epithelial cells lose their cell polarity and cell-tocell adhesion, and acquire migratory and invasive abilities to become mesenchymal stem cells (MSC). These MSCs are multipotent stromal cells capable of differentiating into various cell types and trigger the phenotypic transition from an epithelial to a mesenchymal state. Therefore, EMT promotes migration and survival during cancer metastasis and confers stemness features to particular subsets of cells. Furthermore, a major problem limiting our ability to treat PDAC is the existence of rare populations of pancreatic cancer stem cells (PCSCs) or cancer-initiating cells in pancreatic tumors. PCSCs may represent sub-populations of tumor cells resistant to therapy which are most crucial for driving invasive tumor growth. These cells are capable of regenerating the cellular heterogeneity associated with the primary tumor when xenografted into mice. Therefore, the presence of PCSCs has prognostic relevance and influences the therapeutic response of tumors. PCSCs express markers of cancer stem cells (CSCs) including CD24, CD133, CD44, and epithelial specific antigen as well as the drug transporter ABCG2 grow as spheroids in a defined growth medium. A major difficulty in studying tumor cell dissemination and metastasis has been the identification of markers that distinguish metastatic cancer cells from cells that are normally circulating in the bloodstream or at sites where these cells metastasize. Evidence highlights a linkage between CSC and EMT. In this review, The current understanding of the PCSCs, signaling pathways regulating these cells, PDAC heterogeneity, EMT mechanism, and links between EMT and metastasis in PCSCs

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“…Lentiviral-mediated shRNA interference was performed as described previously (26). Wnt5a expression was knocked down in SW480 or TAMs by transduction of a lentiviral vector expressing a short hairpin RNA-Wnt5a shRNA (sh-Wnt5a) or negative control shRNA (sh-NC) (Genechem, China).…”

Section: Cell Transfectionmentioning

confidence: 99%

Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression

Liu

Yang

Wang

et al. 2020

Preprint

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Background: Tumor-associated macrophages (TAMs) in the tumor microenvironment influence tumor initiation, invasion and metastasis. Several studies have shown that Wnt5a is mainly expressed in the tumor stroma, especially in TAMs. However, whether Wnt5a regulates the polarization and biological function of TAMs in colorectal cancer (CRC) is incompletely understood. Methods: Immunofluorescence staining was performed to detect CD68 and Wnt5a expression in colorectal tissues from patients (63 CRC specimens VS 20 normal tissues). RT-qPCR, flow cytometry, ELISA and inhibitors were carried out to explore the role of Wnt5a in the polarization of TAMs. Clone formation and transwell assays were performed to determine the effects of Wnt5a–treated macrophages on tumor proliferation, migration and invasion in vitro. Finally, a xenograft model was applied to confirm the effects of Wnt5a + TAMs on CRC tumorigenesis. Results: We found that high Wnt5a + CD68 + /CD68 + TAMs ratio was significantly associated with poor prognosis in CRC patients and Wnt5a + TAM was an M2-like TAM subtype. Subsequently, we found that Wnt5a induced macrophages to secrete IL-10, which then acted as an autocrine cytokine to induce M2 polarization of these macrophages. IL-10 neutralizing antibody completely reversed the pro-M2 effect of Wnt5a. Mechanistically, the CaKMII-ERK1/2-STAT3 pathway was required for Wnt5a-mediated IL-10 expression in macrophages. Furthermore, Wnt5a-induced M2 macrophages promoted CRC cells proliferation, migration and invasion; knockdown of Wnt5a in TAMs significantly impaired the pro-tumor functions of TAMs. Conclusions: Our data indicate that Wnt5a could induce M2 polarization of TAMs by regulating CaKMII-ERK1/2-STAT3 pathway–mediated IL-10 secretion, ultimately promoting tumor growth and metastasis of CRC.

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Macrophage-expressed CD51 promotes cancer stem cell properties via the TGF-β1/smad2/3 axis in pancreatic cancer

Cited by 53 publications

References 38 publications

Wnt5a/CaMKII/ERK/CCL2 axis is required for tumor-associated macrophages to promote colorectal cancer progression

Wnt5a/CaMKII/ERK/CCL2 axis is required for tumor-associated macrophages to promote colorectal cancer progression

Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance

Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression

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