Table 2.

Potential roles of tenascin-C during tissue repair and tumorigenesis

Stage	Function		Key References
Inflammation	Adaptive immunity	Promotes lymphocyte migration	Clark et al. 1997
		Stimulates Th2 cell activation	Nakahara et al. 2006
		Inhibits T cell activation	Kuznetsova and Roberts 2004
	Innate immunity	Inhibits myeloid cell migration	Loike et al. 2001; Talts et al. 1999; Midwood et al. 2009
		Stimulates TLR4 mediated cytokine production
	Re-epithelialization	Keratinocyte adhesion and migration	Matsuda et al. 1999; Katz et al. 2006; Ishii et al. 2008
		Epithelial cytodifferentiation
Tissue rebuilding	Cell migration	ECM-cell interactions	Chiquet-Ehrismann and Chiquet 2003; Tran 2005
		GFR activation
	Cell proliferation	GRF activation	Swindle et al. 2001
	ECM synthesis	Cell response to growth factors	El-Karef et al. 2007
		Synthesis of GF	Nakao et al. 1998
	ECM assembly	Cross linking of ECM	Lundell et al. 2004
	Angiogenesis	EC adhesion and migration	Chung et al. 1996
		Cell response to growth factors	Murphy-Ullrich et al. 1991
		Release of EPCs from bone marrow	Ballard et al. 2006
		Serum levels of VEGFA in tumor mice	Tanaka et al. 2004
Tissue remodelling	Wound contraction	Myofibroblast differentiation, migration, contraction	Tamaoki et al. 2005
	Cell clearance	Stimulates apoptosis	Nakao et al. 1998; Wallner et al. 2004
Metastasis	Cancer cells: reduced adhesion, enhanced proliferation	Inhibition of syndecan-4	Huang et al. 2001;
		Activation of Wnt signaling	Ruiz et al. 2004
		Induction of EDNRA	Lange et al. 2007
	Cancer cells: enhanced migration and invasion	Enhanced migration in response to promigratory factors	Lange et al. 2008
		Induction of MMPs	Tremble et al. 1994; Kalembeyi et al. 2003; Imai et al. 1994; Siri et al. 1995; Watanabe et al. 2000
		Cleavage by MMPs
	Cancer cells: increased dissemination and homing	Downregulated expression blocks lung metastasis	Tavazoie et al. 2008; Calvo et al. 2008
		Present in matrix channels of metastatic melanomas	Kaariainen et al. 2006
		Present in matrix conduits of the thymus	Drumea-Mirancea et al. 2006
	Carcinoma associated fibroblasts	Secrete tenascin-C and HGF; necessary for invasion of colorectal carcinomas	De Wever et al. 2004
		Lumen formation and secretion of tenascin-C into tubes	Gaggioli et al. 2007

Tenascin-C can influence a wide variety of physiological processes during tissue repair and cancer. Tenascin-C exhibits context-specific regulation of innate and adaptive immune cell function during the early inflammatory phase, and stimulates the subsequent re-epithelialization, tissue rebuilding, and tissue remodeling by promoting cell migration and proliferation, ECM synthesis and assembly, angiogenesis, wound contraction and cell death during tissue repair. During tumor angiogenesis, invasion and metastasis tenascin-C induces pro-migratory and pro-proliferative signaling, activates MMPs and is expressed in matrix channels that are associated with metastastic cancer. ECM, extracellular matrix, EDNRA, endothelin receptor type A, EPC, endothelial progenitor, GFR, growth factor receptor, Th2, T helper cells, TLR, toll like receptor