Collagen Type I: A Substrate and a Signal for Invasion

Alpha-catenin is required for IGF-I-induced cellular migration but not invasion in human colonic cancer cells

“…Thus, we can conclude that a-catenin is not required for IGF-I-induced invasion. Our finding that cells, when dropped on type-I collagen gels react to IGF-I even in the absence of a-catenin, is in line with the concept that type-I collagen functions not only as a substratum but also as a proinvasive signaling substratum (Van Hoorde et al, 2000). Along with this notion, pancreatic cancer cells dramatically reduce E-cadherin gene expression when cultured on type-I collagen, leading to increased proliferation and migration behavior (Menke et al, 2001).…”

“…Moreover, when exposed to extracellular matrix during invasion, carcinoma cells do not possess the adhesion apparatus characteristic for normal cells, and can invade despite a low level of a-catenin (Glukhova et al, 1995). It is clear that IGF-I is not the unique cofactor necessary to stimulate invasion, since various extrinsic factors have similar effects on some epithelial cancer cells from various origins (Van Hoorde et al, 2000;Steelant et al, 2001). However, our experiments clearly indicate that IGF-I should be considered as a potent and efficient paracrine host factor triggering invasion during colon cancer progression.…”

“…Invasion of cancer cells from various tissue origins is often inversely related to the expression of E-cadherin (Van Hoorde et al, 2000). According to this, neither LoVo cells nor HCT-8 cells invade type-I collagen without the addition of external stimuli other than the collagen itself.…”

Role of tissue stroma in cancer cell invasion

“…Myofibroblasts provide pro-invasive signals in a combinatorial fashion, meaning that they produce several cytokines, chemokines, and inflammatory mediators [37,148] that in combination affect invasion of the cancer cells. Fine tuning the quantity of ECM proteins, proteinases, and proteinase inhibitors provides structural scaffolding for cancer cells and sends specific signals that affect the expression of genes that are implicated in cytoskeletal organization, ectopic survival, and differentiation [149,150]. Since myofibroblasts also are potentially invasive, it is worthwhile to ask who is invading whom in the ecosystem of a primary cancer [17].…”

Inhibition of fibroblast to myofibroblast transition by halofuginone contributes to the chemotherapy-mediated antitumoral effect

“…Collagen type I accumulation has been observed at the tumor-stroma boundary (2,14), and the TGF-h -dependent activation of neighboring stroma cells leads to a survival advantage and increased metastasis formation (15). Collagen type I has been hypothesized to be a signal for invasion, and its intratumoral expression level has been associated with increased tumor invasiveness (16,17). The association of collagen type I with stellate cell activation -associated protein, also known as cytoglobin (Cygb/STAP), which has been hypothesized to regulate collagen synthesis under the control of TGF-h, is characteristic of cells that exhibit an activated phenotype (18,19).…”