Abstract
Intratumoral fibrosis is a histologic manifestation of fibrotic tumor stroma. The interaction between cancer cells and fibrotic stroma is intricate and reciprocal, involving dysregulations from multiple biological processes. Different components of tumor stroma are implicated via distinct manners. In the kidney, intratumoral fibrosis is frequently observed in renal cell carcinoma (RCC). However, the underlying mechanisms remain largely unclear. In this review, we recapitulate evidence demonstrating how fibrotic stroma interacts with cancer cells and mechanisms shared between RCC tumorigenesis and renal fibrogenesis, providing promising targets for future studies.
Highlights
Renal fibrosis is the common outcome of different chronic kidney diseases (CKDs), characterized by excessive accumulation of extracellular matrix (ECM) and disrupted renal microarchitecture (Hewitson, 2009)
We introduce how fibrotic stroma interacts with tumor cells in different organs: (1) the interplay between fibrotic stroma and cancer cells via metabolic manners; (2) how signaling mediates features of fibronectin (FN) and enzymes regulating collagen exert a protumor effect; (3) robust reciprocal communications between cancer cells and cancer-associated fibroblasts (CAFs) mediated by secretory molecules; (4) demonstration of the pro-inflammatory feature of CAFs and the controversial involvement of ECM in tumor immunity
epithelial– mesenchymal transition (EMT) and its secretory mediator TGF-β1 have been identified in two renal diseases repeatedly; in Renal cell carcinoma (RCC), there has been no study conducted to determine whether EMT caused by tumor stroma is capable of facilitating RCC tumorigenesis
Summary
Renal fibrosis is the common outcome of different chronic kidney diseases (CKDs), characterized by excessive accumulation of extracellular matrix (ECM) and disrupted renal microarchitecture (Hewitson, 2009). MiR-200a and miR-141 were shown to abrogate EMT of tubular epithelial cells by targeting ZEB1 and ZEB2, revealing an anti-fibrotic effect of the miR-200 family (Jung et al, 2009) This evidence demonstrated that miR-200 family was involved in mediating the transcriptional repressor of E-cadherin and induction of EMT, leading to RCC and renal fibrosis separately. Several studies identified engagement of multiple miRNAs including miR-382 (Kriegel et al, 2010), miR-23a (Xu et al, 2018), and miR-133b and 199b (Sun et al, 2018) in renal fibrogenesis or tumorigenesis via EMT, suggesting EMT as a promising target to bridge two diseases Both classes are well-established to exert a certain influence on various biological processes, and the interactions among them are coming into the view (Yoon et al, 2014). In vivo and in vitro miRNA, microRNAs; TGF, transforming growth epithelial–mesenchymal transition
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
