Abstract
The enrichment of cancer-associated fibroblast (CAFs) in a tumor microenvironment (TME) cultivates a pro-tumorigenic niche via aberrant paracrine signaling and matrix remodeling. A favorable niche is critical to the maintenance of cancer stem cells (CSCs), a population of cells that are characterized by their enhanced ability to self-renew, metastasis, and develop therapy resistance. Mounting evidence illustrates the interplay between CAF and cancer cells expedites malignant progression. Therefore, targeting the key cellular components and factors in the niche may promote a more efficacious treatment. In this study, we discuss how CAF orchestrates a niche that enhances CSC features and the potential therapeutic implication.
Highlights
Tumors are illustrated as “wounds that do not heal” due to the enrichment of fibroblasts and immune cells at the tumor site, which highly mimics that of an inflammatory response of a nonneoplastic tissue (Dvorak, 1986)
Studies demonstrated IL6 derived from prostate cancer cells elicits pro-tumor fibroblast activation protein (FAP)+cancer-associated fibroblast (CAFs) (Giannoni et al, 2010)
Given vitamins are essential for healthy tissue and their toxicity is relatively lower compared to chemotherapy, repurposing vitamin analogs to rewire activated fibroblast into a quiescent state may present a viable therapeutic strategy that can be translated into the clinical settings
Summary
Tumors are illustrated as “wounds that do not heal” due to the enrichment of fibroblasts and immune cells at the tumor site, which highly mimics that of an inflammatory response of a nonneoplastic tissue (Dvorak, 1986). Studies demonstrated IL6 derived from prostate cancer cells elicits pro-tumor FAP+CAF (Giannoni et al, 2010) These FAP+ CAF secretes MMP2 and MMP9 to potentiate EMT and stemness genes. MMP3 that is predominantly produced by fibroblast (Witty et al, 1995) is demonstrated to promote stem cell population by enhancing canonical Wnt signaling, potentially leading to hyperplastic growth of normal tissues (Kessenbrock et al, 2013), depicting fibroblast can contribute to tumor initiation via ECM remodeling. CAF-derived exosomal long non-coding RNA (lncRNA) H19 was exhibited to enable stemness expression by sponging miR-141 that targets β-catenin (Ren et al, 2018) Another mechanism that CAF mediates chemoresistance resides in its ability to remodel the ECM. Breast cancer Non-small cell lung cancer and colon cancer Colorectal cancer Prostate carcinoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
