首页|Untangling the tumorigenic role of homotrimeric collagen I
Untangling the tumorigenic role of homotrimeric collagen I
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Pancreatic ductal adenocarcinoma is characterized by a complex microenvironment. In this issue of Cancer Cell, Chen and colleagues define an oncogenic role of tumor-cell-produced collagen I homotrimers, wherein tumor development is promoted by integrin alpha3/beta1 -dependent activation of tumor cell signaling and modulation of tumor microbiome and immunity. Solid tumors develop as abnormal tissue ecosystems with an irregular extracellular matrix (ECM) that establishes a bio-physically and biochemically pro-tumori-genic environment (Cox, 2021). This is particularly evident in pancreatic ductal adenocarcinoma (PDAC), in which the majority of the tumor is made up of host stromal cells and an abundant ECM, such that malignant cells constitute less than 15% of the tumor on average (Ho et al., 2020). Pleiotropic tumor-promoting effects have been ascribed to the stiffened ECM, and these effects include activation of mechano-signaling pathways to augment oncogenic signaling, retention of growth factors and cytokines to alter local biochemical signaling pathways, supplying nutrients for tumor cells, and driving an increase in the interstitial pressure that collapses vessels and thus impedes blood flow (Ho et al., 2020).
Claus J?rgensen
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Systems Oncology, Cancer Research UK Manchester Institute, University of Manchester, Alderley Park
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