Irradiation of melanoma cells induced changes in the S100A4-RAGE interaction toward a promigratory phenotype


Irradiation of melanoma cells induced changes in the S100A4-RAGE interaction toward a promigratory phenotype

Haase, C.; Wolf, S.; Pietzsch, J.

Aim:

Tumor metastasis is responsible for most cancer deaths, and can occur after long periods of tumor dormancy. The treatment of metastases would be either radiation only or surgery combined with adjunctive postoperative radiation therapy. Multiple reports have focused on the role of S100A4 in cancer progression, specifically its ability to enhance metastasis. We suggest that RAGE (receptor for advanced glycation endproducts) is a putative receptor for S100A4.
However, the role of S100A4‐RAGE interaction in melanoma metastasis is still unclear. The aim of this study was to characterize molecular and cellular mechanism of irradiated B16‐F10 melanoma cells, thereby, examining changes in the S100A4‐RAGE interaction and the ability for migration of irradiated melanoma cells in the presence of tumor associated macrophages.

Material and Methods:

B16‐F10 cells were exposed to single dose irradiation (5 Gy, 20 Gy) and mouse RAW 264.7 cells were used as a model for tumor‐associated macrophages. The expression of S100A4 and RAGE was quantified via real‐time RT‐PCR and Western‐blot analysis. Furthermore, cell migration was investigated with irradiated B16‐F10 cells in a 24‐transwell chamber for 16 h and 24 h. Migration was influenced by seeding RAW cells as a chemoattractant into the lower
compartments and recombinant S100A4 as a stimulus to the upper compartments. Migratory cells were labeled with Calcein‐AM and quantified in a standard fluorescence microplate reader.

Results:

The total number of vital irradiated B16‐F10 cells is significantly decreased with increasing dose up to 20 Gy and up to six days, thereby altering their morphological appearance. Expression of S100A4 and RAGE is significantly increased in surviving B16‐F10 cells three and six days after 20 Gy (p[[Unsupported Character ‐ ]]0.05). Furthermore, irradiated B16‐F10 cells have a higher migratory activity supposed due to an enhanced expression of S100A4 and RAGE. RAW cells and/or recombinant S100A4 caused a further increasing migration activity of irradiated cells (20 Gy).

Conclusions:

There is a close association of melanoma cells and macrophages with alterations of their migratory and invasive activity after irradiation. We suppose a perpetual para‐/autocrine expression mechanism of extracellular S100A4 and RAGE,
and thereby changing functional properties of melanoma cells towards a promigratory phenotype. This study was supported in part by the Deutsche Forschungsgemeinschaft (grant Pi 304/1‐1).

  • Poster
    Annual Congress of the European Association of Nuclear Medicine (EANM, 11.-15.10.2008, München, Deutschland
  • Abstract in refereed journal
    European Journal of Nuclear Medicine and Molecular Imaging 35(2008), S316
    DOI: 10.1007/s00259-008-0896-9

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Publ.-Id: 11858