Fibroblast nemosis induces angiogenic responses of endothelial cells

Journal Article · Wed Mar 10 04:00:00 EST 2010 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2009.11.012· OSTI ID:22209873

Enzerink, Anna ^[1]; Rantanen, Ville ^[2]; Vaheri, Antti ^[1]

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1. Haartman Institute, University of Helsinki, P.O. BOX 21, FIN-00014 Helsinki (Finland)
2. Computational Systems Biology Laboratory, Institute of Biomedicine and Genome-Scale Biology Research Program, University of Helsinki, P.O. BOX 63, 00014 Helsinki (Finland)

Increasing evidence points to a central link between inflammation and activation of the stroma, especially of fibroblasts therein. However, the mechanisms leading to such activation mostly remain undescribed. We have previously characterized a novel type of fibroblast activation (nemosis) where clustered fibroblasts upregulated the production of cyclooxygenase-2, secretion of prostaglandins, proteinases, chemotactic cytokines, and hepatocyte growth factor (HGF), and displayed activated nuclear factor-{kappa}B. Now we show that nemosis drives angiogenic responses of endothelial cells. In addition to HGF, nemotic fibroblasts secreted vascular endothelial growth factor (VEGF), and conditioned medium from spheroids promoted sprouting and networking of human umbilical venous endothelial cells (HUVEC). The response was partly inhibited by function-blocking antibodies against HGF and VEGF. Conditioned nemotic fibroblast medium promoted closure of HUVEC and human dermal microvascular endothelial cell monolayer wounds, by increasing the motility of the endothelial cells. Wound closure in HUVEC cells was partly inhibited by the antibodies against HGF. The stromal microenvironment regulates wound healing responses and often promotes tumorigenesis. Nemosis offers clues to the activation process of stromal fibroblasts and provides a model to study the part they play in angiogenesis-related conditions, as well as possibilities for therapeutical approaches desiring angiogenesis in tissue.

• OSTI ID: 22209873
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 5 Vol. 316; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANGIOGENESIS
ANIMAL TISSUES
ANTIBODIES
ANTIGENS
CATTLE
FIBROBLASTS
INFLAMMATION
LYMPHOKINES
MACROPHAGES
NEOPLASMS
PROSTAGLANDINS
RECEPTORS
VEINS
WOUNDS