Abstract B16: Extracellular S100A4 as an inducer of a cytokine network that mediates tumor-stroma crosstalk: Potential implications for metastases

Among soluble factors that appear to be of high importance for metastasis progression are chemokines from the S100 family. One such factor is S100A4, a small calcium binding protein linked to metastasis and poor prognosis in several cancer types. The protein is expressed in and secreted from not only tumor cells, but also various stroma cells, suggesting that S100A4 might be an important factor in the tumor microenvironment. Recently we have revealed that in vivo S100A4-positive stroma cells are tightly associated with the metastatic nodules in the brain and lungs, suggesting the role of S100A4 in facilitating metastatic growth in these microenvironments. How S100A4 executes its metastasis-promoting functions is however not fully elucidated. Here we hypothesize that the extracellular S100A4 can trigger a cytokine network that mediates the tumor-stroma crosstalk and thereby facilitates metastases progression in malignant melanoma. We have shown that extracellular S100A4 stimulates melanoma cells to secrete various cytokines and growth factors, including IL-8, IL-6, CXCL2, sICAM-1 and VEGF, molecules playing a role in cancer progression and angiogenesis in particular. Since cytokines can act in a paracrine manner, they can mediate interactions between tumor cells and stroma cells. Thus, we have shown that conditioned medium from melanoma cells treated with extracellular S100A4 modulates the angiogenic functions of endothelial cells making them more migratory and more proned to make vascular-like networks in vitro. Among factors induced by S100A4 were also pro-inflammatory cytokines associated with macrophage recruitment and/or activation. Currently we are investigating whether the S100A4-triggered cytokines modulate the properties of macrophages making them support tumor cells. Altogether, our results indicate a potential role of S100A4 in stimulating tumor-stoma crosstalk which might mimic the formation of a metastatic niche-like milieu facilitating metastases. Citation Format: Ingrid J. Bettum, Kotryna Vasiliauskaite, Solveig J. Pettersen, Gunhild M. Malandsmo, Lina Prasmickaite. Extracellular S100A4 as an inducer of a cytokine network that mediates tumor-stroma crosstalk: Potential implications for metastases. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B16.