The cancer-inhibitory effects of proliferating tumor-residing fibroblasts.

Autor: Delinassios JG; International Institute of Anticancer Research, 1(st) km Kapandritiou-Kalamou Rd., Kapandriti, 19014 Attica, Greece. Electronic address: jg.delinassios@gmail.com., Hoffman RM; Department of Surgery, University of California, 9300 Campus Point Drive, La Jolla, CA 92037, USA; AntiCancer Inc., 7917 Ostrow St, San Diego, CA 92111, USA. Electronic address: all@anticancer.com.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Reviews on cancer [Biochim Biophys Acta Rev Cancer] 2022 Jan; Vol. 1877 (1), pp. 188673. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1016/j.bbcan.2021.188673
Abstrakt: Initiation, local progression, and metastasis of cancer are associated with specific morphological, molecular, and functional changes in the extracellular matrix and the fibroblasts within the tumor microenvironment (TME). In the early stages of tumor development, fibroblasts are an obstacle that cancer cells must surpass or nullify to progress. Thus, in early tumor progression, specific signaling from cancer cells activates bio-pathways, which abolish the innate anticancer properties of fibroblasts and convert a high proportion of them to tumor-promoting cancer-associated fibroblasts (CAFs). Following this initial event, a wide spectrum of gene expression changes gradually leads to the development of a stromal fibroblast population with complex heterogeneity, creating fibroblast subtypes with characteristic profiles, which may alternate between being tumor-promotive and tumor-suppressive, topologically and chronologically in the TME. These fibroblast subtypes form the tumor's histological landscape comprising areas of cancer growth, inflammation, angiogenesis, invasion fronts, proliferating and non-proliferating fibroblasts, cancer-cell apoptosis, fibroblast apoptosis, and necrosis. These features reflect general deregulation of tissue homeostasis within the TME. This review discusses fundamental and current knowledge that has established the existence of anticancer fibroblasts within the various interacting elements of the TME. It is proposed that the maintenance of fibroblast proliferation is an essential parameter for the activation of their anticancer capacity, similar to that by which normal fibroblasts would be activated in wound repair, thus maintaining tissue homeostasis. Encouragement of research in this direction may render new means of cancer therapy and a greater understanding of tumor progression.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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