ED-B fibronectin expression is a marker of epithelial-mesenchymal transition in translational oncology

Abstract

Fibronectin is a component of the extracellular matrix that links collagen fibers to integrins on the cell's surface. The splicing isoforms, containing the ED-B domain, are not expressed in adult tissues but only in tumor stroma or during embryonic development. Fibroblasts and endothelial cells express ED-B fibronectin during angiogenesis. Also cancer cells can synthetize ED-B fibronectin, but its function in tumor growth needs to be further elucidated.We evaluated the expression of ED-B fibronectin in prostate cancer cell lines: PC3 and DU145. Using TGF-β, we induced epithelial to mesenchymal transition in culture and observed an increase of ED-B fibronectin expression. Thereafter, we evaluated the expression of ED-B fibronectin in multipotent mesangiogenic progenitor cells, and in mesenchymal stromal cells. The expression of ED-B fibronectin was much higher in mesenchymal than prostate cancer cells even after the epithelial to mesenchymal transition.Epithelial to mesenchymal transition is a key step for tumor progression contributing to the metastatic spread. Therefore, circulating cancer cells could seed into the metastatic niche taking advantage from the ED-B fibronectin that secrete their own.

Magnetic resonance molecular imaging of metastatic breast cancer by targeting extradomain‐B fibronectin in the tumor microenvironment

“…TGFβ is known to induce EMT and transform epithelial breast cancer cells into invasive mesenchymal cells. As shown in Figure 1a, EDB-FN mRNA levels increased in TGFβ treated 4T1 and MDA-MB-231 cells, consistent with the role of EDB-FN as a marker of EMT (17). EDB-FN was also highly expressed in 4T1 tumor tissues (Figure S1).…”

“…EDB-FN contains an extra type III domain insertion between III 7 and III 8 domain, leading to conformational changes related to fibronectin matrix assembly(16). EDB-FN overexpression is a marker of epithelial-to-mesenchymal transition (EMT) (17), a biological process associated with cancer metastasis and drug resistance (18). It is highly expressed in the ECM of aggressive prostate tumors of high metastatic potential, low in low-risk prostate tumors of low metastatic potential (15).…”

Role of the extracellular matrix in cancer‐associated epithelial to mesenchymal transition phenomenon

“…Noteworthy, specific modifications in FN structure are directly correlated to the onset of EMT. An illustrative example is that the expression of the FN splicing isoform EdB, specific for tumor tissues, is suggested to be a marker of EMT in translational oncology (Petrini et al, ; Yi et al, ).…”

Interactions Between Tumor Biology and Targeted Nanoplatforms for Imaging Applications

“…EDB‐FN is absent in adult blood vessels, but is overexpressed during angiogenesis in normal and neoplastic tissues, making it an attractive marker for angiogenesis 51. EDA‐FN can also act as a marker of normal and tumor vasculature.…”