Project C4

Regulation of Leukocyte Recruitment by Intra- and Peritumoral Endothelial Cells in HCC

Principal Investigators: PD Dr. Eduard Ryschich


Short Summary

Although the contributing role of the immune system in HCC is accepted, exact mechanisms of leukocyte recruitment into HCC tissue are poorly understood. Our previous studies showed that endothelium of HCC has a dysregulated and pro-inflammatory phenotype and that leukocyte recruitment occurs mainly from peritumoral blood vessels. The current proposal aims to study mechanisms which control differential leukocyte recruitment in intratumoral and in peritumoral HCC tissue. We will focus on the role of endothelial cell adhesion molecules and will use an innovative technology of 4D intravital microscopy.


List of relevant publications

  1. Shirouzu Y, Ryschich E, Salnikova O, Kerkadze V, Schmidt J, Engelmann G (2009) Rapamycin inhibits proliferation and migration of hepatoma cells in vitro. J Surg Res (in press).
  2. Nussbaum T, Samarin J, Ehemann V, Bissinger M, Ryschich E, Khamidjanov A, Yu X, Gretz N, Schirmacher P, Breuhahn K (2008) Autocrine insulin-like growth factor-II stimulation of tumor cell migration is a progression step in human hepatocarcinogenesis. Hepatology 48:146-56.
  3. Ryschich E, Lizdenis P, Ittrich C, Benner A, Stahl S, Hamann A, Schmidt J, Knolle P, Arnold B, Hammerling G J, Ganss R (2006) Molecular fingerprinting and autocrine growth regulation of endothelial cells in a murine model of hepatocellular carcinoma. Cancer Research 66:198-11.
  4. Ryschich E, Marten A, Schmidt E, Linnebacher M, Wentzensen N, Eisold S, Klar E, Buchler M W, Schmidt J (2006) Activating anti-CD40 antibodies induce tumour invasion by cytotoxic T-lymphocytes and inhibition of tumour growth in experimental liver cancer. Eur.J.Cancer 42:981-87.
  5. Ryschich E, Kerkadze V, Lizdenis P, Paskauskas S, Knaebel H P, Gross W, Gebhard M M, Buchler M W, Schmidt J (2006) Active leukocyte crawling in microvessels assessed by digital time-lapse intravital microscopy. J Surg Res 135:291-96.
  6. Maksan SM, Schmidt E, Ryschich E, Harms W, Schmidt J (2005) Enhancement of leukocyte adhesion after percutaneous irradiation in rats with hepatocellular carcinoma. World J.Gastroenterol 11:1991-94.
  7. Maksan SM, Araib PM, Ryschich E, Gebhard MM, Schmidt J (2004) Immune escape mechanism: defective resting and stimulated leukocyte-endothelium interaction in hepatocellular carcinoma of the rat. Dig Dis Sc 49:859-65.
  8. Ryschich E, Schmidt E, Maksan S M, Klar E, Schmidt J (2004) Expansion of endothelial surface by an increase of vessel diameter during tumor angiogenesis in experimental and hepatocellular and pancreatic cancer. World J Gastroenterol 10:3171-74.
  9. Maksan SM, Paulo H, Ryschich E, Kuntz C, Gebhard MM, Klar E, Schmidt J (2003) In vivo assessment of angioarchitecture and microcirculation in experimental liver cancer: a new model in rats. Dig Dis Sci 48:279-90.
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