Molecular Pathways: Connecting Fibrosis and Solid Tumor Metastasis

Abstract

Pathologic organ fibrosis is a condition that can affect all major tissues and is typically ascribed to the excessive accumulation of extracellular matrix components, predominantly collagens. It typically leads to compromise of organ function and subsequent organ failure, and it is estimated that 45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection of fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases.

Microsphere cytometry to interrogate microenvironment-dependent cell signaling

“…Fibrosis is considered an initiating stage of cancer development (Cox & Erler 2014). Mammography measures tissue density in the breast, and indicates the level of fibrosis.…”

Multi-Channel Optical Coherence Elastography Using Relative and Absolute Shear-Wave Time of Flight

“…The cellular microenvironment plays a critical role in cancer initiation, progression, and the ability to invade and metastasise [1,2]. In particular, the stiffness of the extracellular matrix (ECM) regulates cellular processes, including proliferation, alignment, adhesion, morphology, motility, lineage commitment, differentiation state, and resistance to apoptosis [3–6].…”

Structural ECM components in the premetastatic and metastatic niche

“…Furthermore, changes in matrix stiffness and fibrosis, the excessive deposition of fibrous ECM components (mainly collagen), have been implicated in tumor progression (21). The process of converting physical signals into biological responses is known as mechanotransduction (115).…”

“…In the primary tumor the combined effects of leaky blood and lymphatic vessels, proliferation of cancer cells, and elevated deposition and remodeling of ECM components hinder proper fluid drainage, raising the interstitial pressure leading to increased stiffness (47,73,87,108,117). A detailed discussion of changes in stiffness and in mechanotransduction upon matrix changes in tumorigenesis has been covered elsewhere (21,28,47,54,72,107) and is beyond the scope of this review.…”

“…Any measurements of premetastatic niches will be difficult as any changes in structure are minute and because it will only become a metastatic niche upon the arrival and colonization of metastatic cells, which is challenging to monitor (21). The careful dissection of components and structural changes in premetastatic and metastatic niches will possibly be aided by the development of nanoparticles, such as polymer dots, coupled to sensors that are able to measure alterations in force and stiffness in the future.…”