Tumor-associated collagen signatures: pushing tumor boundaries

Abstract

In 2006, a new model of invasive breast tumor emerged and, since 2011, is gaining recognition and research momentum. "Tumor-associated collagen signatures" describe 3 distinct layers of collagen which radiate outward in shells from the main body of the tumor. The outermost layer (TACS3) features branches of collagen radiating away from the tumor, 90°perpendicular to the tumor surface. TACS3 increases tumor span and correlates directly with metastasis, though presently difficult to detect in breast tissue. TACS is an emerging model but has been validated by multiple labs in vitro and in vivo, specifically for breast cancer prognostics. Newly recognized and accepted tumor borders will impact both R0 resections and downstream surgical reconstruction. This review aims to comprehensively introduce and connect the ranging literature on linearized collagen of invasive tumor borders. Using PubMed keyword searches containing "aligned," "linear," "oriented," and "organized," we have gathered the studies on TACS, integrated the concept into the clinic, and projected future platforms.

Navigating the Collagen Jungle: The Biomedical Potential of Fiber Organization in Cancer

“…A number of groups, including our own, have investigated the best computational approaches to quantify changes in collagen fiber organization in a wide range of biomedical applications. The main features that were found to be meaningful to date are collagen fiber amount or density [57,58], orientation and anisotropy of orientations (or alignment) [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]. Among all of these features, collagen fiber orientation and alignment were of most interest to investigators.…”

Toward the development of portable light emitting diode‐based polarization spectroscopy tools for breast cancer diagnosis

“…The malignant breast tissues are more disordered and heterogeneous due to infiltration and tumor cell proliferation, leading to multiple gradients and discontinuities in the refractive indexes [6, 26, 47–50]. This results in a higher density of the scattering microstructures in the malignant breast tissue, contributing to a higher scattering than adjacent normal breast tissue [8, 51].…”

Human Breast Extracellular Matrix Microstructures and Protein Hydrogel 3D Cultures of Mammary Epithelial Cells

“…TAC-3 has been found to be related to invasive breast lesion types and worse prognosis compared to those lesions without the TAC-3 characteristics [ 47 ]. In the past 15 years, clinical evidence has confirmed the TACS [ 47 , 48 , 49 , 50 ]. Our decellularized normal breast ECM and breast tumor ECM imaging analyses not only clearly confirmed all the TACS phenotypes described above ( Figure 1 a(iv) vs. Figure 1 a(ii)), but also introduced additional cancer-associated ECM features, at least for the IDC type of tumors.…”