All three genes were associated with a poor prognosis in human patients and high levels of SERPINB5, secreted by cancer cells and deposited in the ECM, correlated with poor patient prognosis. AGRN promoted EMT in primary tumors, whereas SERPINB5 and CSTB enhanced late steps in the metastatic cascade by elevating invadopodia formation and in vivo extravasation. Furthermore, these proteins operate at different metastatic steps. Using both overexpression and knockdown experiments, we demonstrate that all three are promoters of PDAC metastasis. Here we studied three cancer-cell-derived matrisome proteins that are significantly overrepresented during PDAC progression AGRN (agrin), SERPINB5 (serine protease inhibitor B5), and CSTB (cystatin B). In marked contrast, those derived from cancer cells correlate strongly with poor survival. Consistent with that observation, we previously showed that individual matrisome proteins derived from stromal cells correlate with either long or short patient survival. However, non-selective depletion of ECM has led to poor patient outcomes. The abundant extracellular matrix (ECM) in PDAC comprises a major fraction of the tumor mass and plays various roles in promoting resistance to therapies. The prognosis for pancreatic ductal adenocarcinoma (PDAC) remains poor despite decades of effort.
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