Display options
Cite
Eefsen RL, Engelholm L, Alpizar-Alpizar W, et al. Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy. Cancer Microenviron. 2015;8(2):93-100doi: 10.1007/s12307-015-0172-z.
Eefsen, R. L., Engelholm, L., Alpizar-Alpizar, W., Van den Eynden, G. G., Vermeulen, P. B., Christensen, I. J., Laerum, O. D., Rolff, H. C., Høyer-Hansen, G., Vainer, B., Osterlind, K., & Illemann, M. (2015). Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy. Cancer microenvironment : official journal of the International Cancer Microenvironment Society, 8(2), 93-100. https://doi.org/10.1007/s12307-015-0172-z
Eefsen, R L, et al. "Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy." Cancer microenvironment : official journal of the International Cancer Microenvironment Society vol. 8,2 (2015): 93-100. doi: https://doi.org/10.1007/s12307-015-0172-z
Eefsen RL, Engelholm L, Alpizar-Alpizar W, Van den Eynden GG, Vermeulen PB, Christensen IJ, Laerum OD, Rolff HC, Høyer-Hansen G, Vainer B, Osterlind K, Illemann M. Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy. Cancer Microenviron. 2015 Aug;8(2):93-100. doi: 10.1007/s12307-015-0172-z. Epub 2015 Aug 14. PMID: 26268716; PMCID: PMC4542827.
Copy Download .nbib Format: NLM
Share it on

Cancer Microenviron. 2015 Aug;8(2):93-100. doi: 10.1007/s12307-015-0172-z. Epub 2015 Aug 14.

Inflammation and uPAR-Expression in Colorectal Liver Metastases in Relation to Growth Pattern and Neo-adjuvant Therapy.

Cancer microenvironment : official journal of the International Cancer Microenvironment Society

R L Eefsen, L Engelholm, W Alpizar-Alpizar, G G E Van den Eynden, P B Vermeulen, I J Christensen, O D Laerum, H C Rolff, G Høyer-Hansen, B Vainer, K Osterlind, M Illemann

Affiliations

  1. The Finsen Laboratory, Rigshospitalet, Ole Maaløs Vej 5, 3rd floor, Copenhagen, Denmark, [email protected].

PMID: 26268716 PMCID: PMC4542827 DOI: 10.1007/s12307-015-0172-z

Abstract

Proteolytic activity and inflammation in the tumour microenvironment affects cancer progression. In colorectal cancer (CRC) liver metastases it has been observed that three different immune profiles are present, as well as proteolytic activity, determined by the expression of urokinase-type plasminogen activator (uPAR).The main objectives of this study were to investigate uPAR expression and the density of macrophages (CD68) and T cells (CD3) as markers of inflammation in resected CRC liver metastases, where patients were neo-adjuvantly treated with chemotherapy with or without the angiogenesis inhibitor bevacizumab. Chemonaive patients served as a control group. The markers were correlated to growth patterns (GP) of liver metastases, i.e. desmoplastic, pushing and replacement GP. It was hypothesised that differences in proteolysis and inflammation could reflect tumour specific growth and therapy related changes in the tumour microenvironment. In chemonaive patients, a significantly higher level of uPAR was observed in desmoplastic liver metastases in comparison to pushing GP (p = 0.01) or replacement GP (p = 0.03). A significantly higher density of CD68 was observed in liver metastases with replacement GP in comparison to those with pushing GP (p = 0.01). In liver metastases from chemo treated patients, CD68 density was significantly higher in desmoplastic GP in comparison to pushing GP (p = 0.03). In chemo and bevacizumab treated patients only a significant lower CD3 expression was observed in liver metastases with a mixed GP than in those with desmoplastic (p = 0.01) or pushing GP (p = 0.05). Expression of uPAR and the density of macrophages at the tumour margin of liver metastasis differ between GP in the untreated patients. A higher density of T cells was observed in the bevacizumab treated patients, when desmoplastic and pushing metastases were compared to liver metastases with a mix of the GP respectively, however no specific correlations between the immune markers of macrophages and T cells or GP of liver metastases could be demonstrated.

References

  1. Cancer Res. 1994 Aug 1;54(15):4065-71 - PubMed
  2. Int J Cancer. 2009 Apr 15;124(8):1860-70 - PubMed
  3. Nat Rev Cancer. 2009 Apr;9(4):239-52 - PubMed
  4. Exp Cell Res. 2013 Jul 1;319(11):1596-603 - PubMed
  5. Cell. 2010 Mar 19;140(6):883-99 - PubMed
  6. Contrib Microbiol. 2006;13:118-37 - PubMed
  7. Clin Chem. 2010 Oct;56(10):1636-40 - PubMed
  8. Ann Surg Oncol. 2009 Sep;16(9):2524-30 - PubMed
  9. J Pathol. 2014 Jan;232(2):199-209 - PubMed
  10. Cancer Res. 2013 Apr 1;73(7):2031-43 - PubMed
  11. Nature. 2002 Dec 19-26;420(6917):860-7 - PubMed
  12. Cancer Immunol Immunother. 1993 Jul;37(2):125-30 - PubMed
  13. J Immunother Emphasis Tumor Immunol. 1994 Jan;15(1):42-52 - PubMed
  14. J Immunol. 2010 Jan 1;184(1):512-20 - PubMed
  15. Clin Exp Metastasis. 2015 Apr;32(4):369-81 - PubMed
  16. J Transl Med. 2012 Jan 03;10:1 - PubMed
  17. Clin Exp Metastasis. 2012 Aug;29(6):541-9 - PubMed
  18. Am J Pathol. 2014 Dec;184(12):3384-93 - PubMed
  19. Ann Surg Oncol. 2013 Mar;20(3):946-55 - PubMed
  20. Int J Cancer. 2016 Apr 1;138(7):1777-84 - PubMed
  21. Cancer Med. 2014 Aug;3(4):855-64 - PubMed
  22. Cancer Res. 2011 Sep 1;71(17):5670-7 - PubMed
  23. Front Biosci (Elite Ed). 2015 Jan 01;7:293-308 - PubMed
  24. Nat Rev Cancer. 2002 Mar;2(3):161-74 - PubMed
  25. Nature. 2006 May 25;441(7092):444-50 - PubMed
  26. Cell Death Differ. 2014 Jan;21(1):15-25 - PubMed
  27. Immunotherapy. 2013 May;5(5):533-45 - PubMed
  28. Ann Oncol. 2007 Feb;18(2):299-304 - PubMed
  29. Curr Pharm Des. 2003;9(19):1499-528 - PubMed
  30. Breast Cancer Res Treat. 1995 Mar;33(3):199-207 - PubMed
  31. Cancer Immunol Immunother. 2005 Nov;54(11):1143-52 - PubMed
  32. Mod Pathol. 2014 Dec;27(12):1641-8 - PubMed
  33. Cell Res. 2013 Feb;23(2):179-81 - PubMed
  34. Cancer Microenviron. 2008 Dec;1(1):113-29 - PubMed
  35. J Natl Cancer Inst. 1999 May 19;91(10):869-74 - PubMed
  36. Cell Cycle. 2006 Aug;5(16):1760-71 - PubMed
  37. J Pathol. 2001 Oct;195(3):336-42 - PubMed
  38. Am J Clin Pathol. 1994 Dec;102(6):835-41 - PubMed
  39. Cell. 2006 Jan 27;124(2):263-6 - PubMed
  40. Cell. 2010 Apr 2;141(1):39-51 - PubMed
  41. Cancer Immunol Res. 2014 Jun;2(6):530-7 - PubMed
  42. Cancer Cell. 2012 Mar 20;21(3):309-22 - PubMed
  43. J Oncol. 2012;2012:907971 - PubMed

Publication Types