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Fibroblasts in the Tumor Microenvironment: Shield or Spear?

Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Biomedicum, Solnavägen 9, SE-17177 Stockholm, Sweden
Department of Biology, College of Science, Salahaddin University, Irbil 44002, Kurdistan-Iraq
Research Programs Unit, Genome-Scale Biology and Medicum, University of Helsinki, and Helsinki University Hospital, P.O. Box 63, FI-00014 Helsinki, Finland
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(5), 1532;
Received: 15 April 2018 / Revised: 15 May 2018 / Accepted: 16 May 2018 / Published: 21 May 2018
(This article belongs to the Special Issue Tumor Microenvironment)
Tumorigenesis is a complex process involving dynamic interactions between malignant cells and their surrounding stroma, including both the cellular and acellular components. Within the stroma, fibroblasts represent not only a predominant cell type, but also a major source of the acellular tissue microenvironment comprising the extracellular matrix (ECM) and soluble factors. Normal fibroblasts can exert diverse suppressive functions against cancer initiating and metastatic cells via direct cell-cell contact, paracrine signaling by soluble factors, and ECM integrity. The loss of such suppressive functions is an inherent step in tumor progression. A tumor cell-induced switch of normal fibroblasts into cancer-associated fibroblasts (CAFs), in turn, triggers a range of pro-tumorigenic signals accompanied by distraction of the normal tissue architecture, thus creating an optimal niche for cancer cells to grow extensively. To further support tumor progression and metastasis, CAFs secrete factors such as ECM remodeling enzymes that further modify the tumor microenvironment in combination with the altered adhesive forces and cell-cell interactions. These paradoxical tumor suppressive and promoting actions of fibroblasts are the focus of this review, highlighting the heterogenic molecular properties of both normal and cancer-associated fibroblasts, as well as their main mechanisms of action, including the emerging impact on immunomodulation and different therapy responses. View Full-Text
Keywords: normal fibroblasts; cancer-associated fibroblasts; neighbor suppression; cancer; desmoplasia; therapy normal fibroblasts; cancer-associated fibroblasts; neighbor suppression; cancer; desmoplasia; therapy
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Alkasalias, T.; Moyano-Galceran, L.; Arsenian-Henriksson, M.; Lehti, K. Fibroblasts in the Tumor Microenvironment: Shield or Spear? Int. J. Mol. Sci. 2018, 19, 1532.

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