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Cancer Cell Int. 2014 May 16;14:41. doi: 10.1186/1475-2867-14-41. eCollection 2014.

The role of cancer-associated fibroblasts, solid stress and other microenvironmental factors in tumor progression and therapy resistance.

Author information

1
Laboratory of Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
2
Department of Pediatrics and Laboratory of Experimental Medicine, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
3
School of Cancer Sciences, University of Birmingham, Birmingham, UK.

Abstract

Tumors are not merely masses of neoplastic cells but complex tissues composed of cellular and noncellular elements. This review provides recent data on the main components of a dynamic system, such as carcinoma associated fibroblasts that change the extracellular matrix (ECM) topology, induce stemness and promote metastasis-initiating cells. Altered production and characteristics of collagen, hyaluronan and other ECM proteins induce increased matrix stiffness. Stiffness along with tumor growth-induced solid stress and increased interstitial fluid pressure contribute to tumor progression and therapy resistance. Second, the role of immune cells, cytokines and chemokines is outlined. We discuss other noncellular characteristics of the tumor microenvironment such as hypoxia and extracellular pH in relation to neoangiogenesis. Overall, full understanding of the events driving the interactions between tumor cells and their environment is of crucial importance in overcoming treatment resistance and improving patient outcome.

KEYWORDS:

Cancer associated fibroblasts; Interstitial fluid pressure; Solid stress; Therapy resistance; Tumor microenvironment

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