We have located links that may give you full text access.
A landscape of patient-derived cancer-associated fibroblast signals in endometrial cancers.
In conversation with endometrial tumor cells, the endometrial cancer-associated fibroblasts (CAFs) are the "partners in crime" of uterine neoplasm's highly heterogeneous tumor microenvironment (TME). We designed a laboratory-friendly method to culture endometrial CAFs on a patient-to-patient basis for studying the CAF-TME and CAF-tumor cell interaction(s). Here, we present a comprehensive characterization of endometrial CAFs derived from patients' tumor tissues (T) and tumor-adjacent normal tissues (N). We used more than 80 T and N from 53 consecutive consented patients with endometrial cancers at the Avera Cancer Institute. We derived TCAF and NCAF in a non-enzymatic feeder-layer culture and characterized their expression of markers by qRT-PCR, flow cytometry, immunocytochemistry, immunofluorescence, and Western blot. Although similar in the expression pattern of EpCAM-/CK18-/vimentin+ as in ovarian CAFs, endometrial NCAFs, and TCAFs characteristically presented dual morphology in culture. Endometrial CAFs were EpCAM-/CK18-/CD45-/CD31-/SMA+/TE-7+/PDGFRA+/CXCL12+/Meflin+/CD155+/CD90+ with patient-specific positivity for S100A4/FAP/PD-L1/CD44. Endometrial CAFs expressed mRNAs for signaling proteins of several pathways and receptor-ligands, including (1) cell cycle pathway, (2) TGF pathway, (3) FGF pathway, (4) Wnt-beta-catenin pathway, (5) HER pathway, (6) tyrosine kinase receptor ligands, and (7) steroid receptors. We tested the hypoxic response of CAFs to show that endometrial CAFs upregulate MMP1 in a HIF-1a-independent manner. In trying to delineate the relationship between expressions of CAF markers and T-cells in the tumor tissue, we observed that FAP-positive CAFs that are derived from CD4/CD8 positive tumor tissue expressed CXCL12 mRNA. The data indicate the role of the CXCL12-CXCR4 pathway of the CAF-rich stroma in the lymphocytic infiltration of the tumor. We demonstrate that endometrial CAFs can be cultured in an enzymatic-digestion-independent manner, and their signaling landscape can be mapped toward understanding CAF-TME dialogue. Our data will help unearth the functional relevance of endometrial CAFs in the context of clinical outcomes and designing CAF-inclusive therapy in the future.
Full text links
Related Resources
Trending Papers
Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.Endocrine Reviews 2024 April 28
The Tricuspid Valve: A Review of Pathology, Imaging, and Current Treatment Options: A Scientific Statement From the American Heart Association.Circulation 2024 April 26
Intravenous infusion of dexmedetomidine during the surgery to prevent postoperative delirium and postoperative cognitive dysfunction undergoing non-cardiac surgery: a meta-analysis of randomized controlled trials.European Journal of Medical Research 2024 April 19
Interstitial Lung Disease: A Review.JAMA 2024 April 23
Management of Diverticulitis: A Review.JAMA Surgery 2024 April 18
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app