Science Note
[Oct. 15, 2024] Previous Science Note
Cancer cells hijack macrophages to metastasis
Recent research into cancer metastasis shows that cancer cells hijack immune cells, particularly macrophages, to promote metastasis. Here are some of the papers showing how macrophages contribute to cancer metastasis and immune evasion. Cancer metastasis is the spread of cancer cells from a primary tumor to distant organs, often evading immune surveillance. Immune cells, such as macrophages, can be co-opted by cancer cells to create an immunosuppressive environment that supports tumor growth and metastasis. Tumor-associated macrophages (TAMs) and other immune cells such as neutrophils and regulatory T cells can promote metastatic progression by facilitating tissue remodeling, angiogenesis and immune evasion. Conversely, enhancing the function of cytotoxic immune cells, such as CD8+ T cells and natural killer (NK) cells, may help to target and eliminate metastatic cancer cells. |
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Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis |
Necroptosis enhances ‘don’t eat me’ signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis |
Mesothelin Secretion by Pancreatic Cancer Cells Co-opts Macrophages and Promotes Metastasis |
Point of Interest - In pancreatic ductal adenocarcinoma (PDAC), macrophage reprogramming by efferocytosis supports pancreatic cancer liver metastasis, allowing cancer cells to evade immune detection and grow. - Macrophage progranulin regulates lysosomal acidification, which is critical for efferocytosis and macrophage conversion during metastasis. - Blocking efferocytosis or progranulin improves CD8+ T cell function and reduces liver metastasis, suggesting new therapeutic approaches. |
Point of Interest - Mixed lineage kinase domain like pseudo kinase-driven necroptosis in PDAC recruits macrophages, enhances the tumor CD47 "don't eat me" signal and induces CXCL8 activation. - Necroptosis-induced CXCL8 activation initiates epithelial-mesenchymal transition and endothelial adhesion, promoting PDAC liver metastasis. - Blocking necroptosis and CD47 reduces PDAC liver metastasis, offering potential for neoadjuvant immunotherapy and radical surgery. |
Point of Interest - Mesothelin secretion by PDAC cells reprograms macrophages by inducing macrophage VEGFA and S100A9 expression. - Macrophage-derived VEGFA supports tumor growth, while S100A9 promotes neutrophil infiltration and lung metastasis. - Mesothelin drives macrophage-neutrophil interactions and promotes PDAC metastasis through extracellular traps and VEGFA signaling. |
Related Techniques | ||
Apoptosis detection in multiple samples | Annexin V Apoptosis Plate Assay Kit | |
Phagocytosis Assay | AcidSensor Labeling Kit – Endocytic Internalization Assay and Cellstain- Calcein-AM solution | |
Endocytosis Detection detection | ECGreen-Endocytosis Detection | |
Lysosomal function | Lysosomal Acidic pH Detection Kit -Green/Red and Green/Deep Red | |
First-time autophagy research | Autophagic Flux Assay Kit | |
Plasma Membrane Staining | PlasMem Bright Green / Red | |
Total ROS detection | Highly sensitive DCFH-DA or Photo-oxidation Resistant DCFH-DA | |
Glycolysis/Oxidative phosphorylation Assay | Glycolysis/OXPHOS Assay Kit | |
Cell Proliferation / Cytotoxicity Assay | Cell Counting Kit-8, Cytotoxicity LDH Assay Kit-WST | |
Related Applications | ||
Phagocytosis assay of labeled apoptotic cells in THP-1 cells |
Wortmannin is known to inhibit endosomal recycling and lysosomal translocation, leading to endosomal enlargement. ①Eary endosome: Rab5-RFP (red) As a result, it was confirmed that ECGreen (green) co-localizes only with enlarged early endosomes and recycling endosomes (Fig. ① and ②), but not with late endosomes or Lysosomes (Fig. ③ and ④), supporting Wortmannin's effect. ECGreen can visualize changes in the intracellular vesicular trafficking system and endosome shape. Endosomes (ECGreen, green): Ex. 405 nm / Em. 500 – 560 nm [Experimental Procedure] |
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Accurate Measurement for Lysosomal pH changesExisting lysosomal pH detection reagents have issues with dye localization, pH sensitivity, and retention. pHLys Green is a dye that solves these issues. The improved dye retention and localization enable detection of normal lysosomes, and the improved pH sensitivity enables detection of slight pH changes. |
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1. High sensitive pH detection Comparison of pH response of cells treated with low concentrations of lysosomal acidification inhibitor Bafilomycin A1 |
2. High specificity for lysosomes Comparison of specificity for lysosomes using lysosomal marker protein LAMP1-GFP expressing cells |
3. High retention in lysosomes Comparison of intracellular retention |
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