Abstract
Recent research has highlighted the importance of key tumor microenvironment features, notably the collagen-rich extracellular matrix (ECM) in characterizing tumor invasion and progression. This led to great interest from both basic researchers and clinicians, including pathologists, to include collagen fiber evaluation as part of the investigation of cancer development and progression. Fibrillar collagen is the most abundant in the normal extracellular matrix, and was revealed to be upregulated in many cancers. Recent studies suggested an emerging theme across multiple cancer types in which specific collagen fiber organization patterns differ between benign and malignant tissue and also appear to be associated with disease stage, prognosis, treatment response, and other clinical features. There is great potential for developing image-based collagen fiber biomarkers for clinical applications, but its adoption in standard clinical practice is dependent on further translational and clinical evaluations. Here, we offer a comprehensive review of the current literature of fibrillar collagen structure and organization as a candidate cancer biomarker, and new perspectives on the challenges and next steps for researchers and clinicians seeking to exploit this information in biomedical research and clinical workflows.
Highlights
The main features that were found to be meaningful to date are collagen fiber amount or density [57,58], orientation and anisotropy of orientations [46,59], individual fiber properties including angle, width, length and curvature, texture analysis-based collagen fiber patterns [10,60,61,62], fiber network branching [63], and features related to combined analysis of collagen fibers and their associated tumor cells such as tumor-associated collagen signatures [8,46,64]
The role of fibrillar collagen in disease, in oncologic diseases, is less well understood even though the extracellular matrix (ECM) often forms a major component of the tumor microenvironment
There is growing evidence that changes in fibrillar collagen organization greatly contribute to the important role of the ECM in cancer invasion and progression
Summary
The tumor microenvironment consists of multiple biochemical, mechanical, and structural signals. One of the major structural components of the tumor microenvironment is the extracellular matrix (ECM). The ECM is a very dynamic structure consisting of many components including collagen, laminin, fibronectin, glycoproteins, proteoglycans, and polysaccharides (Figure 1). There have been increasing efforts to better understand the influences of the ECM components on cell behaviors and functions. A major focus of studying the ECM is the role of collagen in both normal and abnormal function. Collagen is the most abundant ECM protein in the human body. There are twenty-eight different types of collagen involved in many normal biological functions such as tissue scaffolding, Bioengineering 2021, 8, 17.
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