Extracellular Matrix Alterations in Metastatic Processes

Abstract

The extracellular matrix (ECM) is a complex network of extracellular-secreted macromolecules, such as collagen, enzymes and glycoproteins, whose main functions deal with structural scaffolding and biochemical support of cells and tissues. ECM homeostasis is essential for organ development and functioning under physiological conditions, while its sustained modification or dysregulation can result in pathological conditions. During cancer progression, epithelial tumor cells may undergo epithelial-to-mesenchymal transition (EMT), a morphological and functional remodeling, that deeply alters tumor cell features, leading to loss of epithelial markers (i.e., E-cadherin), changes in cell polarity and intercellular junctions and increase of mesenchymal markers (i.e., N-cadherin, fibronectin and vimentin). This process enhances cancer cell detachment from the original tumor mass and invasiveness, which are necessary for metastasis onset, thus allowing cancer cells to enter the bloodstream or lymphatic flow and colonize distant sites. The mechanisms that lead to development of metastases in specific sites are still largely obscure but modifications occurring in target tissue ECM are being intensively studied. Matrix metalloproteases and several adhesion receptors, among which integrins play a key role, are involved in metastasis-linked ECM modifications. In addition, cells involved in the metastatic niche formation, like cancer associated fibroblasts (CAF) and tumor associated macrophages (TAM), have been found to play crucial roles in ECM alterations aimed at promoting cancer cells adhesion and growth. In this review we focus on molecular mechanisms of ECM modifications occurring during cancer progression and metastatic dissemination to distant sites, with special attention to lung, liver and bone. Moreover, the functional role of cells forming the tumor niche will also be reviewed in light of the most recent findings.

Myxoid stroma is associated with postoperative relapse in patients with stage II colon cancer

“…2 Relapse-free survival rates in NMY group and MY group Fig. 3 Overall survival rates in NMY group and MY group extracellular matrix (ECM) remodeling and desmoplasia by increasing the deposition of ECM [20,41]. In several reports, single or small clusters of cancer cells (TB) have been frequently observed at MY areas [25,29], and TB was associated with DR in the present study.…”

Myxoid stroma is associated with postoperative relapse in patients with stage II colon cancer

“…Among cells of the stromal component, broblasts have been termed cancer-associated broblasts (CAFs) and are important promotors of tumor progression and metastasis [40]. CAFs can induce dedifferentiation by extracellular matrix (ECM) remodeling and desmoplasia by increasing the deposition of ECM [41,42]. In several reports, single or small clusters of cancer cells (TB) have been frequently observed at MY areas [25,29], and TB was associated with DR in the present study.…”

The crosstalk between circular RNAs and the tumor microenvironment in cancer metastasis

“…Integrins are the main mechanoreceptors on tumor cells that bind ECM proteins to mediate bidirectional signaling across cell membranes. They couple diverse extracellular ligands to the cytoskeleton [49] and play a key role in metastasis-linked ECM modifications [50]. Integrins consist of two transmembrane glycoproteins, α and β [51].…”