Mechanically stressed cancer microenvironment: Role in pancreatic cancer progression

Matthew Hadden; Anubhav Mittal; Jaswinder Samra; Hala Zreiqat; Sumit Sahni; Yogambha Ramaswamy

doi:10.1016/j.bbcan.2020.188418

Mechanically stressed cancer microenvironment: Role in pancreatic cancer progression

Biochim Biophys Acta Rev Cancer. 2020 Dec;1874(2):188418. doi: 10.1016/j.bbcan.2020.188418. Epub 2020 Aug 20.

Authors

Matthew Hadden¹, Anubhav Mittal², Jaswinder Samra², Hala Zreiqat³, Sumit Sahni⁴, Yogambha Ramaswamy⁵

Affiliations

¹ School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, NSW 2006, Australia.
² Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Kolling Institute of Medical Research, University of Sydney, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia.
³ School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, NSW 2006, Australia; ARC Training Centre for Innovative Bioengineering, The University of Sydney, NSW 2006, Australia; The University of Sydney Nano Institute, The University of Sydney, Sydney, NSW 2006, Australia.
⁴ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Australia; Kolling Institute of Medical Research, University of Sydney, Australia; Australian Pancreatic Centre, St Leonards, Sydney, Australia. Electronic address: sumit.sahni@sydney.edu.au.
⁵ School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, NSW 2006, Australia; The University of Sydney Nano Institute, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: yogambha.ramaswamy@sydney.edu.au.

PMID: 32827581
DOI: 10.1016/j.bbcan.2020.188418

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies in the world due to its insensitivity to current therapies and its propensity to metastases from the primary tumor mass. This is largely attributed to its complex microenvironment composed of unique stromal cell populations and extracellular matrix (ECM). The recruitment and activation of these cell populations cause an increase in deposition of ECM components, which highly influences the behavior of malignant cells through disrupted forms of signaling. As PDAC progresses from premalignant lesion to invasive carcinoma, this dynamic landscape shields the mass from immune defenses and cytotoxic intervention. This microenvironment influences an invasive cell phenotype through altered forms of mechanical signaling, capable of enacting biochemical changes within cells through activated mechanotransduction pathways. The effects of altered mechanical cues on malignant cell mechanotransduction have long remained enigmatic, particularly in PDAC, whose microenvironment significantly changes over time. A more complete and thorough understanding of PDAC's physical surroundings (microenvironment), mechanosensing proteins, and mechanical properties may help in identifying novel mechanisms that influence disease progression, and thus, provide new potential therapeutic targets.

Keywords: Mechanical properties; Mechanotransduction; Pancreatic ductal adenocarcinoma; Pancreatic tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Carcinoma, Pancreatic Ductal / metabolism*
Disease Progression
Extracellular Matrix / metabolism
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks*
Humans
Mechanotransduction, Cellular
Neoplasm Metastasis
Pancreatic Neoplasms / metabolism*
Tumor Microenvironment