Skip to main content
SpringerLink
Log in

The Inflammatory Tissue Microenvironment and the Early Stages of Malignancy

  • Chapter
  • First Online:
Pre-Invasive Disease: Pathogenesis and Clinical Management

  • 353 Accesses

Abstract

The microenvironment has a critical impact on the malignant potential and eventual outcome of a pre-invasive lesion. A tumour-promoting microenvironment contains many of the cells and mediators of chronic inflammation. The origins of this may be extrinsic i.e. inflammatory stimuli cause or exacerbate the evolution of cells with malignant potential, or intrinsic i.e. the oncogenic changes in the initiated cells induce inflammatory pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444

    Article  PubMed  CAS  Google Scholar 

  2. Ruffell B, DeNardo DG, Affara NI, Coussens LM (2010) Lymphocytes in cancer development: polarization towards pro-tumor immunity. Cytokine Growth Factor Rev 21:3–10

    Article  PubMed  CAS  Google Scholar 

  3. Borrello MG, Alberti L, Fischer A, Degl’innocenti D, Ferrario C, Gariboldi M, Marchesi F, Allavena P, Greco A, Collini P et al (2005) Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. PNAS 102:14825–14830

    Article  PubMed  CAS  Google Scholar 

  4. De Falco V, Gastellone MD, De Vita G, Cirafici AM, Hershman JM, Guerrero C, Fusco A, Melillo RM, Santoro M (2007) RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small GTPase. Cancer Res 67:381–390

    Article  PubMed  Google Scholar 

  5. Guerra C, Schuhmacher AJ, Canamero M, Grippo PJ, Verdaguer L, Perez-Gallego L, Dubus P, Sandgren EP, Barbacid M (2007) Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11:291–302

    Article  PubMed  CAS  Google Scholar 

  6. Sparmann A, Bar-Sagi D (2004) Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell 6:447–458

    Article  PubMed  CAS  Google Scholar 

  7. Shchors K, Shchors E, Rostker F, Lawlor ER, Brown-Swigart L, Evan GI (2006) The Myc-dependent angiogenic switch in tumors is mediated by interleukin 1beta. Genes Dev 20:2527–2538

    Article  PubMed  CAS  Google Scholar 

  8. Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI (2007) Mast cells are required for angiogenesis and macropscopic expansion of Myc-induced pancreatic islet tumors. Nat Med 13:1211–1218

    Article  PubMed  CAS  Google Scholar 

  9. Galban S, Fan J, Martindale JL, Cheadle C, Hoffman B, Woods MP, Temeles G, Brieger J, Decker J, Gorospe M (2003) von Hippel–Lindau protein-mediated repression of tumor necrosis factor alpha translation revealed through use of cDNA arrays. Mol Cell Biol 23:2316–2328

    Article  PubMed  CAS  Google Scholar 

  10. Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W (2003) Chemokine receptor CXCR4 downregulated by von Hippel–Lindau tumour suppressor pVHL. Nature 425: 307–311

    Article  PubMed  CAS  Google Scholar 

  11. Bierie B, Stover DG, Abel TW, Chytil A, Gorska AE, Aakre M, Forrester E, Yang L, Wagner K-U, Moses HL (2008) Transforming growth factor-b regulates mammary carcinoma cell survival and interaction with the adjacent microenvironment. Cancer Res 68:1809–1819

    Article  PubMed  CAS  Google Scholar 

  12. Balkwill, F. (2009). TNF and Cancer: A Timeline. Nat Reviews Cancer, in press.

    Google Scholar 

  13. Dinarello CA (2009) Interleukin-1beta and the autoinflammatory diseases. N Engl J Med 360:2467–2470

    Article  PubMed  CAS  Google Scholar 

  14. Naugler WE, Karin M (2008) The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med 14:109–119

    Article  PubMed  CAS  Google Scholar 

  15. Mantovani A, Savino B, Locati M, Zammataro L, Allavena P, Bonecchi R (2010) The chemokine system in cancer biology and therapy. Cytokine Growth Factor Rev 21:27–39

    Article  PubMed  CAS  Google Scholar 

  16. Balkwill F (2004) The significance of cancer cell expression of CXCR4. Semin Cancer Biol 14:171–179

    Article  PubMed  CAS  Google Scholar 

  17. Iliopoulos D, Hirsch HA, Struhl K (2009) An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139:693–706

    Article  PubMed  CAS  Google Scholar 

  18. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357: 539–545

    Article  PubMed  CAS  Google Scholar 

  19. Maeda S, Kamata H, Luo JL, Leffert H, Karin M (2005) IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell 121:977–990

    Article  PubMed  CAS  Google Scholar 

  20. Naugler, W. E., Sakurai, T., Kim, S., Maeda, S., Kim, K. H., Elsharkawy, A. M., and Karin, M. (2007). Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science In press

    Google Scholar 

  21. Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, Nebelsiek T, Lundgren-May T, Canli O, Schwitalla S et al (2009) gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 15:91–102

    Article  PubMed  CAS  Google Scholar 

  22. Greten FR, Eckman L, Greten TF, Park JM, Li Z-W, Egan LJ, Kagnoff MF, Karin M (2004) IKKb links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–296

    Article  PubMed  CAS  Google Scholar 

  23. Fox JG, Wang TC (2007) Inflammation, atrophy, and gastic cancer. J Clin Invest 117:60–69

    Article  PubMed  CAS  Google Scholar 

  24. Grivennikov SI, Karin M (2010) Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine Growth Factor Rev 21:11–19

    Article  PubMed  CAS  Google Scholar 

  25. Suganuma M, Kuzuhara T, Yamaguchi K, Fujiki H (2006) Carcinogenic role of tumor necrosis factor-a inducing protein of Helicobacter pylori in human stomach. J Biochem Mol Biol 39:1–8

    Article  PubMed  CAS  Google Scholar 

  26. Moore R, Owens D, Stamp G, East N, Holdworth H, Arnott C, Burke F, Pasparakis M, Kollias G, Balkwill FR (1999) Tumour necrosis factor – a deficient mice are resistant to skin carcinogenesis. Nat Med 5:828–831

    Article  PubMed  CAS  Google Scholar 

  27. Andreu P, Johansson M, Affara NI, Pucci F, Tan T, Junankar S, Korets L, Lam J, Tawfik D, DeNardo DG et al (2010) FcRgamma activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell 17:121–134

    Article  PubMed  CAS  Google Scholar 

  28. de Visser KE, Eichten A, Coussens LM (2006) Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 1:24–37

    Article  Google Scholar 

  29. DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM (2009) CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16:91–102

    Article  PubMed  CAS  Google Scholar 

  30. Lin EY, Nguyen AV, Russell RG, Pollard JW (2001) Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 193:727–739

    Article  PubMed  CAS  Google Scholar 

  31. Colombo MP, Piconese S (2009) Polyps wrap mast cells and Treg within tumorigenic tentacles. Cancer Res 69:5619–5622

    Article  PubMed  CAS  Google Scholar 

  32. Gounaris E, Blatner NR, Dennis K, Magnusson F, Gurish MF, Strom TB, Beckhove P, Gounari F, Khazaie K (2009) T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res 69:5490–5497

    Article  PubMed  CAS  Google Scholar 

  33. Cunha GR, Hayward SW, Wang YZ, Ricke WA (2003) Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer 107:1–10

    Article  PubMed  CAS  Google Scholar 

  34. Erez N, Truitt M, Olson P, Hanahan D (2010) Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-kappaB-dependent manner. Cancer Cell 17:135–147

    Article  PubMed  CAS  Google Scholar 

  35. Saadi A, Shannon NB, Lao-Sirieix P, O’Donovan M, Walker E, Clemons NJ, Hardwick JS, Zhang C, Das M, Save V et al (2010) Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers. Proc Natl Acad Sci U S A 107:2177–2182

    Article  PubMed  CAS  Google Scholar 

  36. Garber K (2009) First results for agents targeting cancer-related inflammation. J Natl Cancer Inst 101:1110–1112

    Article  PubMed  Google Scholar 

  37. Balkwill F, Mantovani A (2010) Cancer and inflammation: implications for pharmacology and therapeutics. Clin Pharmacol Ther 87:401–406

    Article  PubMed  CAS  Google Scholar 

  38. Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G (2009) Aspirin, salicylates, and cancer. Lancet 373:1301–1309

    Article  PubMed  CAS  Google Scholar 

  39. Jacobs EJ, Thun MJ, Bain EB, Rodriguez C, Henley SJ, Calle EE (2007) A large cohort study of long-term daily use of adult-strength aspirin and cancer incidence. J Natl Cancer Inst 99:608–615

    Article  PubMed  CAS  Google Scholar 

  40. Markowitz SD (2007) Aspirin and colon cancer – targeting prevention? N Engl J Med 356:2195–2198

    Article  PubMed  CAS  Google Scholar 

  41. Cuzick J, Otto F, Baron JA, Brown PH, Burn J, Greenwald P, Jankowski J, La Vecchia C, Meyskens F, Senn HJ, Thun M (2009) Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol 10:501–507

    Article  PubMed  CAS  Google Scholar 

  42. Steinbach G, Lynch PM, Phillips RKS, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T et al (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342:1946–1952

    Article  PubMed  CAS  Google Scholar 

  43. Epstein, J., Sanderson, I. R., and Macdonald, T. T. (2010). Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies. Br J Nutr, 1-13.

    Google Scholar 

  44. Fujiki H, Suganuma M, Matsuyama S, Miyazaki K (2005) Cancer prevention with green tea polyphenols for the general population, and for patients following cancer treatment. Curr Cancer Ther Rev 1:109–114

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Cancer and Inflammation, Institute of Cancer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Fran Balkwill

Authors
  1. Fran Balkwill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fran Balkwill .

Editor information

Editors and Affiliations

  1. , MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Hills Road, Cambridge, CB20XZ, United Kingdom

    Rebecca C. Fitzgerald

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Balkwill, F. (2011). The Inflammatory Tissue Microenvironment and the Early Stages of Malignancy. In: Fitzgerald, R. (eds) Pre-Invasive Disease: Pathogenesis and Clinical Management. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6694-0_2

Download citation

Publish with us

Policies and ethics

Search

Navigation