Role of Extracellular Matrix in Development and Cancer Progression

Abstract

The immense diversity of extracellular matrix (ECM) proteins confers distinct biochemical and biophysical properties that influence cell phenotype. The ECM is highly dynamic as it is constantly deposited, remodelled, and degraded during development until maturity to maintain tissue homeostasis. The ECM’s composition and organization are spatiotemporally regulated to control cell behaviour and differentiation, but dysregulation of ECM dynamics leads to the development of diseases such as cancer. The chemical cues presented by the ECM have been appreciated as key drivers for both development and cancer progression. However, the mechanical forces present due to the ECM have been largely ignored but recently recognized to play critical roles in disease progression and malignant cell behaviour. Here, we review the ways in which biophysical forces of the microenvironment influence biochemical regulation and cell phenotype during key stages of human development and cancer progression.

Bioengineering a novel 3D in-vitro model to recreate physiological oxygen levels and tumor-immune interactions

“…The increased expression for each of the studied ECMs in the presence of lower oxygen could either be accounted for by an absolute increase in new ECM generation or by an enhanced enzymatic functional cascade resulting in enhanced alignment of the ECMs already present in the matrix environment. But overall, the different ECM levels by BCa cells growing within our 3D-O model reflect the importance of these changes with respect to reported literature about how ECMs can promote and maintain BCa tumor health and cancer progression (97).…”

Metastasis is altered through multiple processes regulated by the E2F1 transcription factor

“…Many of these genes include various collagens, integrins, and cadherins (Figure 7). Previous research has shown a number of collagens to be important for tumor maintenance, angiogenesis, and metastasis [20]. Collagen IV is the major component of the basement membrane, and is comprised of heterogeneous trimers stemming from six COL4A genes.…”

“…Various other proteins including lamanins, integrins, and fibronectin proteins are essential components of the extracellular matrix. The integrity of extracellular matrix, including the basement membrane, have been shown as being important for the early steps of tumor invasion and metastasis [19,20]. Interestingly, a previous report demonstrated a decrease in the number of circulating tumor cells within PyMT E2F1 -/mice, suggesting a disruption to the early steps in the metastatic cascade.…”

Using SERS Tags to Image the Three‐Dimensional Structure of Complex Cell Models

“…This is a key aspect, for example, in the evaluation of promising anticancer drugs,1 to determine the toxicity of a new (nano)material,2 or to study cell metastasis in tumoral systems 3. Furthermore, considering that the extracellular environment plays an important role in cell‐to‐cell communication, being also one of the key components of tumor invasion,4,5 methods to incorporate it in cell cultures are essential toward achieving more physiologically relevant tissue models. One such method is based on allowing cells to grow in 3D, e.g., in spheroids, in which cell‐to‐cell interactions are closer to a real in vivo situation 6,7.…”