Exosome từ đại thực bào liên quan đến khối u thúc đẩy sự di chuyển của tế bào ung thư dạ dày thông qua việc chuyển giao apolipoprotein E chức năng
Tóm tắt
Các đại thực bào liên quan đến khối u (TAMs) là thành phần chính trong môi trường vi mô của khối u và đã được chứng minh là góp phần vào sự hung hãn của khối u. Tuy nhiên, các cơ chế chi tiết liên quan đến tác động thúc đẩy di căn của TAM đối với ung thư dạ dày vẫn chưa được xác định rõ ràng. Ở đây, chúng tôi cho thấy rằng TAMs được làm giàu trong ung thư dạ dày. TAMs có đặc điểm là kiểu hình phân cực M2 và thúc đẩy sự di chuyển của tế bào ung thư dạ dày cả trong môi trường nuôi cấy tế bào (in vitro) và trong cơ thể (in vivo). Hơn nữa, chúng tôi phát hiện rằng các exosome nguồn gốc từ M2 xác định hoạt động pro-di chuyển trung gian của TAM. Sử dụng phổ khối lượng, chúng tôi xác định rằng apolipoprotein E (ApoE) là protein đặc hiệu và hiệu quả cao trong các exosome lấy từ đại thực bào M2. Hơn nữa, TAMs là quần thể tế bào miễn dịch độc đáo biểu hiện ApoE trong môi trường ung thư dạ dày. Tuy nhiên, các exosome lấy từ đại thực bào M2 của chuột
Từ khóa
#đại thực bào liên quan đến khối u #exosome #apolipoprotein E #ung thư dạ dày #động lực học di chuyểnTài liệu tham khảo
Joyce, J. A. & Pollard, J. W. Microenvironmental regulation of metastasis. Nat. Rev. Cancer 9, 239–252 (2009).
Chen, J. et al. CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3. Cancer Cell 19, 541–555 (2011).
Kaneda, M. M. et al. Macrophage PI3Kgamma drives pancreatic ductal adenocarcinoma progression. Cancer Discov. 6, 870–885 (2016).
Wang, F. et al. CD163+ CD14+ macrophages, a potential immune biomarker for malignant pleural effusion. Cancer Immunol. Immunother. 64, 965–976 (2015).
Condeelis, J. & Pollard, J. W. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124, 263–266 (2006).
Wu, W. et al. Three-step method for systematic lymphadenectomy in gastric cancer surgery using the ‘curettage and aspiration dissection technique’ with Peng’s multifunctional operative dissector. World J. Surg. Oncol. 12, 322 (2014).
Lu, W. et al. Long-term clinical outcomes of laparoscopy-assisted distal gastrectomy versus open distal gastrectomy for early gastric cancer: a comprehensive systematic review and meta-analysis of randomized control trials. Medicine 95, e3986 (2016).
Oue, N. et al. Gene expression profile of gastric carcinoma: identification of genes and tags potentially involved in invasion, metastasis, and carcinogenesis by serial analysis of gene expression. Cancer Res. 64, 2397–2405 (2004).
Milane, L., Singh, A., Mattheolabakis, G., Suresh, M. & Amiji, M. M. Exosome mediated communication within the tumor microenvironment. J. Control. Release 219, 278–294 (2015).
Roma-Rodrigues, C., Fernandes, A. R. & Baptista, P. V. Exosome in tumour microenvironment: overview of the crosstalk between normal and cancer cells. Biomed. Res. Int. 2014, 179486 (2014).
Qu, J. L. et al. Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig. Liver Dis. 41, 875–880 (2009).
Hoshino, A. et al. Tumour exosome integrins determine organotropic metastasis. Nature 527, 329–335 (2015).
Lin, L. Y. et al. Tumour cell-derived exosomes endow mesenchymal stromal cells with tumour-promotion capabilities. Oncogene 35, 6038–6042 (2016).
Ying, X. et al. Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages. Oncotarget 7, 43076–43087 (2016).
Charoentong, P. et al. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 18, 248–262 (2017).
Sagar, G. et al. Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue. Gut 65, 1165–1174 (2016).
Becker, A. et al. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell. 30, 836–848 (2016).
Yuan, X. et al. Gelsolin suppresses gastric cancer metastasis through inhibition of PKR-p38 signaling. Oncotarget 7, 53459–53470 (2016).
Yuan, X. et al. ATF3 suppresses metastasis of bladder cancer by regulating gelsolin-mediated remodeling of the actin cytoskeleton. Cancer Res. 73, 3625–3637 (2013).
Mouneimne, G. et al. Differential remodeling of actin cytoskeleton architecture by profilin isoforms leads to distinct effects on cell migration and invasion. Cancer Cell 22, 615–630 (2012).
Huang, Y., Snuderl, M. & Jain, R. K. Polarization of tumor-associated macrophages: a novel strategy for vascular normalization and antitumor immunity. Cancer Cell 19, 1–2 (2011).
Shen, L. et al. M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma. Sci. Rep. 6, 30347 (2016).
Kim, J. & Bae, J. S. Tumor-associated macrophages and neutrophils in tumor microenvironment. Mediat. Inflamm. 2016, 6058147 (2016).
Sethi, N. & Kang, Y. Unravelling the complexity of metastasis—molecular understanding and targeted therapies. Nat. Rev. Cancer 11, 735–748 (2011).
Zhang, L. et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 527, 100–104 (2015).
Luga, V. et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 151, 1542–1556 (2012).
Lazar, I. et al. Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: a novel mechanism linking obesity and cancer. Cancer Res. 76, 4051–4057 (2016).
Baitsch, D. et al. Apolipoprotein E induces antiinflammatory phenotype in macrophages. Arterioscler. Thromb. Vasc. Biol. 31, 1160–1168 (2011).
Macritchie, N. et al. Plasmacytoid dendritic cells play a key role in promoting atherosclerosis in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 32, 2569–2579 (2012).
Pencheva, N. et al. Convergent multi-miRNA targeting of ApoE drives LRP1/LRP8-dependent melanoma metastasis and angiogenesis. Cell 151, 1068–1082 (2012).
Ha, S. A. et al. Dual action of apolipoprotein E-interacting HCCR-1 oncoprotein and its implication for breast cancer and obesity. J. Cell. Mol. Med. 13, 3868–3875 (2009).
Chen, Y. C. et al. Apolipoprotein E is required for cell proliferation and survival in ovarian cancer. Cancer Res. 65, 331–337 (2005).
Niemi, M. et al. Apolipoprotein E and colon cancer. Expression in normal and malignant human intestine and effect on cultured human colonic adenocarcinoma cells. Eur. J. Intern. Med. 13, 37–43 (2002).
Baroni, S. et al. Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts. Cell Death Dis. 7, e2312 (2016).
Getz, G. S. & Reardon, C. A. Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall. J. Lipid Res. 50 Suppl, S156–161 (2009).
Mahley, R. W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240, 622–630 (1988).
Hoe, H. S., Harris, D. C. & Rebeck, G. W. Multiple pathways of apolipoprotein E signaling in primary neurons. J. Neurochem. 93, 145–155 (2005).
Thorpe, L. M., Yuzugullu, H. & Zhao, J. J. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat. Rev. Cancer 15, 7–24 (2015).
Matsuoka, T. & Yashiro, M. The role of PI3K/Akt/mTOR signaling in gastric carcinoma. Cancers 6, 1441–1463 (2014).
Ho, Y. Y. et al. Endogenously expressed apolipoprotein E has different effects on cell lipid metabolism as compared to exogenous apolipoprotein E carried on triglyceride-rich particles. Biochemistry 39, 4746–4754 (2000).
Yasui, W., Oue, N., Ito, R., Kuraoka, K. & Nakayama, H. Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implications. Cancer Sci. 95, 385–392 (2004).
Sakashita, K. et al. Clinical significance of ApoE expression in human gastric cancer. Oncol. Rep. 20, 1313–1319 (2008).
Tjiu, J. W. et al. Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction. J. Invest. Dermatol. 129, 1016–1025 (2009).
Lobb, R. J. et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J. Extracell. Vesicles 4, 27031 (2015).
Yuan, X. et al. Activation of TLR4 signaling promotes gastric cancer progression by inducing mitochondrial ROS production. Cell Death Dis. 4, e794 (2013).