Advertisement

Endogenous Ligand-Induced Activation of TLR4 in Pre-metastatic Phase Is Both Downstream and Upstream of TNF Signaling

  • Yoshiro Maru
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)

Abstract

Recently accumulating information suggests the existence of endogenous TLR4 candidate including hyaluronan fragments, HMGB1, Tenascin, saturated fatty acids, S100A8, etc. (reviewed in [1]). We have added one more candidate SAA3 (serum amyloid A3) [2]. In our experimental metastasis assay, we subcutaneously inject tumor cells that never reach the lungs, which we call pre-metastatic lungs (pre-metastatic phase) [3]. Then we purposely inject labeled tumor cells via the tail vein and count their numbers in the lungs (metastatic phase). A cDNA microarray screening for up-regulated genes in pre-metastatic lungs between tumor-bearing and non-bearing mice gave both S100A8 and SAA3 in the top 50 genes [2, 4]. Surface plasmon resonance analysis of TLR4/MD-2 complex purified from baculovirus and S100A8 or SAA3 purified from mammalian cells provided direct evidence for binding. TLR is a well-studied pattern recognition receptor working as a sensor for bacterial endotoxin or lipopolysaccharide (LPS). S100A8 was initially identified in the synovial fluid of rheumatoid arthritis patients and is one of the members of well-conserved EF-hand Ca2+-binding protein family [5, 6]. SAA3 belong to the SAA family of acute phase reactant [7]. SAA1 and SAA2 are generated in liver in response to inflammation and integrated into HDL (high density lipoprotein). SAA3 is produced extra-hepatically, such as in myeloid cells and endothelial cells. We have shown that S100A8 induces SAA3 expression with promoter activation by two- to fourfolds [2]

Keywords

Inject Tumor Cell Surface Plasmon Resonance Analysis Paracrine Loop Binding Protein Family Endogenous TLR4 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

I thank Dr T. Tomita and Ms S. Ishibashi for helps in experiments. This work was partly supported by Grants-in-Aid for Scientific Research from the Japanese government (No.21117008) (Homeostatic inflammation study group) to Y.M.

References

  1. 1.
    Maru Y (2009) A concept of homeostatic inflammation provided by endogenous TLR4 agonists that function before and after danger signal for metastasis. Anti-Inflammat Anti-Aller Agents Med Chem 8:337–347Google Scholar
  2. 2.
    Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, and Maru Y (2008) The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol 10:1349–1355CrossRefPubMedGoogle Scholar
  3. 3.
    Maru Y (2009) Logical structures extracted from metastasis experiments. Cancer Sci 100:2006–2013Google Scholar
  4. 4.
    Hiratsuka S, Watanabe A, Aburatani H, Maru Y (2006) Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8:1369–1375CrossRefPubMedGoogle Scholar
  5. 5.
    Odink K, Cerletti N, Brüggen J, Clerc RG, Tarcsay L, Zwadlo G, Gerhards G, Schlegel R, Sorg C (1987) Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis. Nature 330:80-82CrossRefPubMedGoogle Scholar
  6. 6.
    Santamaria-Kisiel L, Rintala-Dempsey AC, Shaw GS (2006) Calcium-dependent and -independent interactions of the S100 protein family. Biochem J 396:201–214CrossRefPubMedGoogle Scholar
  7. 7.
    Uhlar CM, Whitehead AS (1999) Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem 265:501–523CrossRefPubMedGoogle Scholar
  8. 8.
    Zhang X, Shan P, Jiang G, and Cohn L, Lee PJ (2006) Toll-like receptor 4 deficiency causes pulmonary emphysema. J Clin Invest 116:3050–3059CrossRefPubMedGoogle Scholar
  9. 9.
    Nagai Y, Garrett KP, Ohta S, Bahrun U, Kouro T, Akira S, Takatsu K, Kincade PW (2006) Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity 24:801–812CrossRefPubMedGoogle Scholar
  10. 10.
    Vogl T, Ludwig S, Goebeler M, Strey A, Thorey IS, Reichelt R, Foell D, Gerke V, Manitz MP, Nacken W, Werner S, Sorg C, Roth J (2004) MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes. Blood 104:4260–4268CrossRefPubMedGoogle Scholar
  11. 11.
    Tisdale MJ (2009) Mechanisms of cancer cachexia. Physiol Rev 89:381–410CrossRefPubMedGoogle Scholar
  12. 12.
    Fujita J, Tsujinaka T, Yano M, Ebisui C, Saito H, Katsume A, Akamatsu K, Ohsugi Y, Shiozaki H, Monden M (1996) Anti-interleukin-6 receptor antibody prevents muscle atrophy in colon-26 adenocarcinoma-bearing mice with modulation of lysosomal and ATP-ubiquitin-dependent proteolytic pathways. Int J Cancer 68:637–643CrossRefPubMedGoogle Scholar
  13. 13.
    Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE (2004) IKKβ/NF-kappaB activation causes severe muscle wasting in mice. Cell 119:285–298CrossRefPubMedGoogle Scholar
  14. 14.
    Moon YS, Kim DH, Song DK (2004) Serum tumor necrosis factor-alpha levels and components of the metabolic syndrome in obese adolescents. Metabolism 53:863–867CrossRefPubMedGoogle Scholar
  15. 15.
    Suganami T, Yuan X, Shimoda Y, Uchio-Yamada K, Nakagawa N, Shirakawa I, Usami T, Tsukahara T, Nakayama K, Miyamoto Y, Yasuda K, Matsuda J, Kamei Y, Kitajima S, Ogawa Y (2009) Activating transcription factor 3 constitutes a negative feedback mechanism that attenuates saturated Fatty acid/toll-like receptor 4 signaling and macrophage activation in obese adipose tissue. Circ Res 105:25–32CrossRefPubMedGoogle Scholar
  16. 16.
    Poitou C, Divoux A, Faty A, Tordjman J, Hugol D, Aissat A, Keophiphath M, Henegar C, Commans S, Clément K (2009) Role of serum amyloid a in adipocyte-macrophage cross talk and adipocyte cholesterol efflux. J Clin Endocrinol Metab 94:1810–1817CrossRefPubMedGoogle Scholar
  17. 17.
    Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 72:3666–3670CrossRefPubMedGoogle Scholar
  18. 18.
    Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, Nacken W, Foell D, van der Poll T, Sorg C, Roth J (2007) Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat Med 13:1042–1049CrossRefPubMedGoogle Scholar
  19. 19.
    Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572CrossRefPubMedGoogle Scholar
  20. 20.
    Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827CrossRefPubMedGoogle Scholar
  21. 21.
    Holzman LB, Marks RM, Dixit VM (1990) A novel immediate-early response gene of endothelium is induced by cytokines and encodes a secreted protein. Mol Cell Biol 10:5830–5838PubMedGoogle Scholar
  22. 22.
    Zhou R (1998) The Eph family receptors and ligands. Pharmacol Ther 77:151–181CrossRefPubMedGoogle Scholar
  23. 23.
    Maru, Y, Hirai, H, Yoshida, MC, Takaku, F (1988) Evolution, expression, and chromosomal location of a novel receptor tyrosine kinase gene, eph. Mol Cell Biol 8:3770–3776PubMedGoogle Scholar
  24. 24.
    Hunter SG, Zhuang G, Brantley-Sieders D, Swat W, Cowan CW, Chen J (2006) Essential role of Vav family guanine nucleotide exchange factors in EphA receptor-mediated angiogenesis. Mol Cell Biol 26:4830–4842CrossRefPubMedGoogle Scholar
  25. 25.
    Parri M, Taddei ML, Bianchini F, Calorini L, Chiarugi P (2009) EphA2 reexpression prompts invasion of melanoma cells shifting from mesenchymal to amoeboid-like motility style. Cancer Res 69:2072–2081CrossRefPubMedGoogle Scholar
  26. 26.
    Okamoto A, Iwamoto Y, Maru Y (2006) Oxidative stress-responsive transcription factor ATF3 potentially mediates diabetic angiopathy. Mol Cell Biol 26:1087–1097CrossRefPubMedGoogle Scholar
  27. 27.
    Masuda J, Usui R, Maru Y (2008) Fibronectin type I repeat is a nonactivating ligand for EphA1 and inhibits ATF3-dependent angiogenesis. J Biol Chem 283:13148–13155CrossRefPubMedGoogle Scholar
  28. 28.
    Gilchrist M, Thorsson V, Li B, Rust AG, Korb M, Roach JC, Kennedy K, Hai T, Bolouri H, Aderem A (2006) Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441:173–178CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of PharmacologyTokyo Women’s Medical UniversityTokyoJapan

Personalised recommendations