Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

The microenvironment factor S100A4 as a modulator of tumor-stroma crosstalk and aggressive phenotype in malignant melanoma (#189)

Lina Prasmickaite 1 , Ingrid Bettum 1 , Kotryna Vasiliauskaite 1 , Solveig Pettersen 1 , Hari Prasad Dhakal 1 , Lars Ahrlund-Richter 2 , Gunhild Mælandsmo 1
  1. Oslo University Hospital, Radium Hospital, Oslo, Norway
  2. Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden

The association of S100-family proteins with metastasis is well known, and recent data links soluble factors from this family to formation of a metastatic niche. One of the family members, S100A4 is a known metastasis-promoting protein, but the molecular mechanisms involved are not completely elucidated. S100A4 is secreted from cancer and stroma cells, and can modulate the microenvironment through induction of matrix-modifying enzymes and effects on stroma cells. Here we hypothesize that S100A4 can execute its pro-metastatic function via modulation of tumor-stroma cell crosstalk, which eventually potentiates metastatic functions and provide tumor cells with survival advantage. By analyzing metastatic melanoma lesions growing in different microenvironments in vivo, we have shown that S100A4-expressing cells localize in the invasive front, where tumor cells interact with the stroma. This suggests that S100A4 participates in the crosstalk between malignant and non-malignant cells in vivo. When soluble S100A4 was added to melanoma cells growing in cultures in vitro or inside lung tissue ex vivo it triggered secretion of pro-inflammatory cytokines like IL-8. The effect was confirmed on many melanoma and non-melanoma cancer cell lines. IL-8 is a significant regulator within tumor microenvironment, able to affect various stroma cells and render therapeutic resistance. To investigate how S100A4-triggered melanoma cells and/or secreted cytokines may modulate tumor-stroma cell crosstalk, we are currently analyzing effects on endothelial cells and macrophages, stroma cells known to be involved in metastases development.