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      Current perspectives of cancer-associated fibroblast in therapeutic resistance: potential mechanism and future strategy

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          Abstract

          The goal of cancer eradication has been overshadowed despite the continuous improvement in research and generation of novel cancer therapeutic drugs. One of the undeniable existing problems is drug resistance due to which the paradigm of killing all cancer cells is ineffective. Tumor microenvironment plays a crucial role in inducing drug resistance besides cancer development and progression. Recently, many efforts have been devoted to understand the role of tumor microenvironment in cancer drug resistance as it provides the shelter, nutrition, and paracrine niche for cancer cells. Cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, reside in symbiotic relationship with cancer cells, supporting them to survive from cancer drugs. The present review summarizes the recent understandings in the role of CAFs in drug resistance in various tumors. Acknowledging the fact that drug resistance depends not only upon cancer cells but also upon the microenvironment niche could guide us to formulate novel cancer drugs and provide the optimal cancer treatment.

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          Most cited references86

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          Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma

          Richard A Moffitt, Raoud Marayati, Elizabeth Flate … (2015)
          Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here, we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, which includes primary, metastatic, and normal samples. By digitally separating tumor, stroma, and normal gene expression, we have identified and validated two tumor-specific subtypes including a “basal-like” subtype which has worse outcome, and is molecularly similar to basal tumors in bladder and breast cancer. Furthermore, we define “normal” and “activated” stromal subtypes which are independently prognostic. Our results provide new insight into the molecular composition of PDAC which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies is critical.
          Article 0 comments Cited 790 times – based on 0 reviews     Review now
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            Stromal gene expression predicts clinical outcome in breast cancer.

            Greg Finak, Nicholas Bertos, François Pépin … (2008)
            Although it is increasingly evident that cancer is influenced by signals emanating from tumor stroma, little is known regarding how changes in stromal gene expression affect epithelial tumor progression. We used laser capture microdissection to compare gene expression profiles of tumor stroma from 53 primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumor-derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node-negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumor progression.
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              Basement membranes: structure, assembly and role in tumour angiogenesis.

              Raghu Kalluri (2003)
              In recent years, the basement membrane (BM)--a specialized form of extracellular matrix (ECM)--has been recognized as an important regulator of cell behaviour, rather than just a structural feature of tissues. The BM mediates tissue compartmentalization and sends signals to epithelial cells about the external microenvironment. The BM is also an important structural and functional component of blood vessels, constituting an extracellular microenvironment sensor for endothelial cells and pericytes. Vascular BM components have recently been found to be involved in the regulation of tumour angiogenesis, making them attractive candidate targets for potential cancer therapies.
              Article 0 comments Cited 405 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Qiong-Zhu Dong: 86-21-5423 7960 , qzhdong@fudan.edu.cn
                Lun-xiu Qin: +86-21-5287172 , qinlx@fudan.edu.cn
                Journal
                Journal ID (nlm-ta): Cell Biol Toxicol
                Journal ID (iso-abbrev): Cell Biol. Toxicol
                Title: Cell Biology and Toxicology
                Publisher: Springer Netherlands (Dordrecht )
                ISSN (Print): 0742-2091
                ISSN (Electronic): 1573-6822
                Publication date (Electronic): 24 January 2019
                Publication date PMC-release: 24 January 2019
                Publication date (Print): 2019
                Volume: 35
                Issue: 5
                Pages: 407-421
                Affiliations
                [1 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, , Fudan University, ; 12 Urumqi Road (M), Shanghai, 200040 China
                [2 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Cancer Metastasis institute, , Fudan University, ; Shanghai, 200040 China
                [3 ]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Institute of Biomedical Sciences, , Fudan University, ; 131 Dong An Road, Shanghai, 200032 China
                Article
                Publisher ID: 9461
                DOI: 10.1007/s10565-019-09461-z
                PMC ID: 6881418
                PubMed ID: 30680600
                SO-VID: 1b728ea5-8a5d-4987-b22c-9569bd2c22a5
                Copyright © © The Author(s) 2019
                License:

                OpenAccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Date received : 12 September 2018
                Date revision received : 15 December 2018
                Date accepted : 3 January 2019
                Funding
                Funded by: National Key Research and Development Program of China
                Award ID: 2017YFC1308604 and 2017YFC0908402
                Funded by: the ?973? State Key Basic Research Program of China
                Award ID: 2014CB542101 and 2013CB910500
                Funded by: National Natural Science Foundation of China (CN)
                Award ID: 81772563, 81672820 and 81372647
                Funded by: China National Key Projects for Infectious Disease
                Award ID: 2012ZX10002-012
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © Springer Nature B.V. 2019

                ScienceOpen disciplines: Cell biology
                Keywords: cancer-associated fibroblast,drug resistance
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: cancer-associated fibroblast, drug resistance

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