Poster No. 160 Differences in the Nemosis Response of Normal and Cancer-associated Fibroblasts

from Patients with Oral Squamous Cell Carcinoma Kati Räsänen 1 , Ismo Virtanen2, Reidar Grenman3, Antti Vaheri1 1 Department of Virology, Haartman Institute, University of Helsinki, Finland, 2 Anatomy, selleck compound Institute of Biomedicine, University of Helsinki, Finland, 3 Head and Neck Surgery, Turku University Central Hospital, Turku, Finland Tumor microenvironment plays a major role in cancer progression and activated fibroblasts, among them cancer-associated fibroblasts (CAFs), are key components of the tumor stroma. Nemosis is a novel type of fibroblast activation induced by cell-cell clustering. Formation of a fibroblast spheroid

causes overexpression of genes involved in selleck inhibitor inflammation and tumor progression, resembling the expression pattern found in CAFs. We used paired normal skin fibroblasts and cancer-associated fibroblasts and primary and recurrent oral squamous cell carcinoma (SCCs) cells. Nemosis response, as observed by induction of COX-2 and VEGF, HGF/SF and selleck products FGF7 and CAF markers a-SMA, FSP1 and FAP differed between these fibroblast populations. One of the normal fibroblast strains, FB-43, upregulated COX-2 in nemosis, but FB-74 cells did not. In contrast, CAF-74 spheroids expressed COX-2 but CAF-43 cells did not. Alpha-SMA protein was expressed in both CAF strains and in FB-74 cells, but not in FB-43 fibroblasts; its mRNA levels were downregulated in nemosis. FSP1 mRNA was downregulated in normal fibroblasts, but not in CAFs, whereas FAP was upregulated in all fibroblasts. Growth factor mRNA levels were upregulated to variable degree. CAFs increased the colony

formation of primary tumor UT-SCC cell lines, but normal fibroblasts inhibited the anchorage-independent growth of recurrent UT-SCC cells. These results clearly demonstrate that fibroblasts Alanine-glyoxylate transaminase obtained from different individuals vary in gene expression and this is reflected in their capability to respond to nemosis. Nemosis, an in vitro model of fibroblast activation, may have its in vivo counterpart in cancer-associated fibroblasts and is a valuable tool in studying the variations between fibroblasts obtained from different individuals. Work on nemosis may also reveal new therapeutic means to modulate unwanted inflammation and tumor progression. Poster No.