gms | German Medical Science

48th Meeting of the Particle Therapy Co-Operative Group

Particle Therapy Co-Operative Group (PTCOG)

28.09. - 03.10.2009, Heidelberg

In vitro evaluation of glioma cell migration after photon and carbon ion radiation therapy

Meeting Abstract

  • S. Rieken - Strahlentherapie und Radioonkologie, Univ.-Klinikum Heidelberg, Heidelberg
  • A. Mohr - Strahlentherapie und Radioonkologie, Univ.-Klinikum Heidelberg, Heidelberg
  • L. Orschiedt - Strahlentherapie und Radioonkologie, Univ.-Klinikum Heidelberg, Heidelberg
  • S. Brons - Heidelberger Ionenstrahl-Therapie (HIT), Heidelberg
  • O. Nairz - Heidelberger Ionenstrahl-Therapie (HIT), Heidelberg
  • M. Winter - Heidelberger Ionenstrahl-Therapie (HIT), Heidelberg
  • T. Haberer - Heidelberger Ionenstrahl-Therapie (HIT), Heidelberg
  • L. Zipp - Strahlentherapie und Radioonkologie, Univ.-Klinikum Heidelberg, Heidelberg
  • J. Debus - Strahlentherapie und Radioonkologie, Univ.-Klinikum Heidelberg, Heidelberg
  • S. Combs - Strahlentherapie und Radioonkologie, Univ.-Klinikum Heidelberg, Heidelberg

PTCOG 48. Meeting of the Particle Therapy Co-Operative Group. Heidelberg, 28.09.-03.10.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09ptcog163

DOI: 10.3205/09ptcog163, URN: urn:nbn:de:0183-09ptcog1630

Veröffentlicht: 24. September 2009

© 2009 Rieken et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: Deep and fast tumor infiltration greatly impairs local control of malignant gliomas, resulting in low cure rates and dismal prognosis. Tumor-associated disturbance of the blood brain barrier facilitates the entry of blood-borne promigratory ligands such as chemokines and phospholipids into the brain tissue. Several authors have shown these ligands to enhance glioma cell motility. Relapses preferentially occur at the leaky tumor margin.

Recently, sublethal photon doses were described to enhance tumor cell migration, therefore, possibly promoting tumor cell infiltration into the adjacent healthy brain. With the exposition of tumor cells to promigratory stimuli in the tumor periphery, a radiogenic increase of glioma cell motility would additionally enhance the risk for local infiltration. Opposed to photon irradiation, carbon ion irradiation was shown to effectively inhibit tumor cell migration even at low doses.

We analysed adhesion and migration in U87 glioma cells attracted by serum gradients and subjected to both photon and carbon ion irradiation.

Material and methods: U87 glioma cells were irradiated with single photon doses of 2, 5, 7, and 10 Gy using 6MV photons at a linear acceleator. Particle radiotherapy was applied with an extended Bragg peak (E=(128±7) MeV/u, LET=(91.5±1.5) keV/μm) at single carbon ion doses of 0.125, 0.5, 2, and 3 Gy at the Heidelberg Ion Therapy Center (HIT). Irradiation was performed 24 hours before initiation of standard microchemotaxis experiments. The chambers were separated by 8 µm pore size polycarbonate membranes coated with collagen IV. Fetal calf serum was used in the lower chamber to attract cells from the upper chamber. After 5 hours of migration, the membranes were stained and analysed microscopically by an investigator blinded to experimental setup.

Results: Photon doses of 2 Gy significantly increased collagen-IV-based glioma cell motilily, but not migration towards a serum gradient. Photon doses of 10 Gy could effectively inhibit both unstimulated tumor cell motility and migration towards serum. Carbon ion irradiation significantly reduced migration of glioma cells both with and without serum exposition. Quantitative analysis of inhibitory effects identified carbon ion irradiation to be equally effective at doses of one third compared to photon irradiation corresponding to a Relative Biological Effectiveness (RBE) of about 3 for U87 glioma cells as shown in our previous experiments (Combs, et al., 2008).

Conclusion: Glioma cell exposition towards serum induces gradient-associated migration and can be inhibited by both photon and carbon ion irradiation in a dose-dependent manner. Unstimulated cell motility is enhanced by low photon doses of 2 Gy, whereas carbon ion doses between 0.125 and 0.5 Gy show no influence on cell migration. Carbon ion single doses of 2 and 3 Gy significantly impair serum-guided tumor cell migration comparable to photon doses of 5 and 7 Gy, respectively.

Initial carbon ion irradiation of the tumor periphery may, therefore, be effective to prevent tumor cell infiltration in areas with promigratory environment.