Gene interactions and pathways from curated databases and text-mining
Biochem Biophys Res Commun 2010, PMID: 20617559

TNF-alpha similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts.

Mueller, Lars; von Seggern, Lena; Schumacher, Jennifer; Goumas, Freya; Wilms, Christian; Braun, Felix; Broering, Dieter C

Cancer-associated fibroblasts (CAFs) represent the predominant cell type of the neoplastic stroma of solid tumors, yet their biology and functional specificity for cancer pathogenesis remain unclear. We show here that primary CAFs from colorectal liver metastases express several inflammatory, tumor-enhancing factors, including interleukin (IL)-6 and monocyte-chemoattractant protein (MCP)-1. Both molecules were intensely induced by TNF-alpha on the transcript and protein level, whereas PDGF-BB, TGF-beta1 and EGF showed no significant effects. To verify their potential specialization for metastasis progression, CAFs were compared to fibroblasts from non-tumor liver tissue. Interestingly, these liver fibroblasts (LFs) displayed similar functions. Further analyses revealed a comparable up-regulation of intercellular adhesion molecule-1 (ICAM-1) by TNF-alpha, and of alpha-smooth muscle actin, by TGF-beta1. Moreover, the proliferation of both cell types was induced by PDGF-BB, and CAFs and LFs displayed an equivalent migration towards HT29 colon cancer cells in Boyden chamber assays. In conclusion, colorectal liver metastasis may be supported by CAFs and resident fibroblastic cells competent to generate a prometastatic microenvironment through inflammatory activation of IL-6 and MCP-1.

Diseases/Pathways annotated by Medline MESH: Colonic Neoplasms, Inflammation, Liver Neoplasms, Neoplasm Metastasis
Document information provided by NCBI PubMed

Text Mining Data

MCP-1 → TNF-alpha: " TNF-alpha similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts "

TNF-alpha → IL-6: " TNF-alpha similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts "

intercellular adhesion molecule-1 → TNF-alpha: " Further analyses revealed a comparable up-regulation of intercellular adhesion molecule-1 ( ICAM-1 ) by TNF-alpha , and of alpha-smooth muscle actin, by TGF-beta1 "

Manually curated Databases

No curated data.