Extracellular Matrix Biomarkers in Colorectal Cancer

Abstract

The cellular microenvironment composition and changes therein play an extremely important role in cancer development. Changes in the extracellular matrix (ECM), which constitutes a majority of the tumor stroma, significantly contribute to the development of the tumor microenvironment. These alterations within the ECM and formation of the tumor microenvironment ultimately lead to tumor development, invasion, and metastasis. The ECM is composed of various molecules such as collagen, elastin, laminin, fibronectin, and the MMPs that cleave these protein fibers and play a central role in tissue remodeling. When healthy cells undergo an insult like DNA damage and become cancerous, if the ECM does not support these neoplastic cells, further development, invasion, and metastasis fail to occur. Therefore, ECM-related cancer research is indispensable, and ECM components can be useful biomarkers as well as therapeutic targets. Colorectal cancer specifically, is also affected by the ECM and many studies have been conducted to unravel the complex association between the two. Here we summarize the importance of several ECM components in colorectal cancer as well as their potential roles as biomarkers.

The Functional Role of Extracellular Matrix Proteins in Cancer

“…Laminins are also involved in cancer progression, including invasion, migration, angiogenesis, metastasis and drug resistance [ 149 , 150 , 151 ]. Expression of various laminin subunits is often upregulated in tumor or stromal cells of malignant tissues.…”

Immune-and Metabolism-Associated Molecular Classification of Ovarian Cancer

“…Studies have implicated the dysregulation of ECM components in OV tumorigenesis and progression and suggested that the elucidation of ECM function in OV is important for developing effective biomarkers and novel drugs ( 53 – 57 ). Studies have also shown that the potential biomarkers of OV metastasis are enriched in ECM-receptor interaction pathway ( 57 ) among other pathways including PI3K/Akt signaling pathway which was also found implicated in the inositol phosphate metabolism as described above. ECM-receptor interaction pathway was also incriminated in the survival and prognosis of high-grade serous OV patients ( 58 – 60 ).…”

mRNAsi-related metabolic risk score model identifies poor prognosis, immunoevasive contexture, and low chemotherapy response in colorectal cancer patients through machine learning

“…According to the GO functional enrichment results, most of these genes were clustered in functional groups related to the extracellular matrix (ECM). The ECM, as the main component of the tumor microenvironment, is considered to play a leading role in the progression of various cancers, including CRC, and promotes the invasion and metastasis of cancer ( 41 – 43 ). In addition, Ortensi et al have demonstrated that the stemness characteristic of cancer tissue contributes to glioma invasiveness, which is closely related to the ECM ( 44 ).…”