Hyaluronan as “Agent Smith” in cancer extracellular matrix pathobiology: Regulatory roles in immune response, cancer progression and targeting

Abstract

Extracellular matrix (ECM) critically regulates cancer cell behavior by governing cell signaling and properties. Hyaluronan (HA) acts as a structural and functional ECM component that mediates critical properties of cancer cells in a molecular size‐dependent manner. HA fragments secreted by cancer‐associated fibroblasts (CAFs) reveal the correlation of HA to CAF‐mediated matrix remodeling, a key step for the initiation of metastasis. The main goal of this article is to highlight the vital functions of HA in cancer cell initiation and progression as well as HA‐mediated paracrine interactions among cancer and stromal cells. Furthermore, the HA implication in mediating immune responses to cancer progression is also discussed. Novel data on the role of HA in the formation of pre‐metastatic niche may contribute towards the improvement of current theranostic approaches that benefit cancer management.

ESR2 Drives Mesenchymal-to-Epithelial Transition in Triple-Negative Breast Cancer and Tumorigenesis In Vivo

“…The complex structure of solid tumors together with the interactions of cancer cells with the surrounding stroma and matrix components stimulate the initiation of a premetastatic niche that promotes metastasis to distant sites (8,(43)(44)(45) (Figure 7A). Alterations in the expression profiles of ECM structural components, including among others, PGs, hyaluronan, growth factor receptors, MMPs, and signaling stimulators, foresee the variations in cancer cell behavior, and construct the homes for metastasis (7,(46)(47)(48). Even though the significance of ERb is less clarified in breast cancer progression than its isoform, ERa, probably due to the existence of several alternatively spliced ERb variants; however, the potential of ERb targeting in aggressive breast cancer subtypes, as TNBC, has gained attention over the years (49).…”

Recreating the extracellular matrix: novel 3D cell culture platforms in cancer research

“…During cancer progression, major components of the provisional matrix reprogram the primary tumour cells and evoke the formation of the premetastatic niche [3]. For instance, HA, the only nonsulfated GAG, is a ubiquitous matrix component comprised of repeated disaccharide units of glucuronic acid and N ‐acetylglucosamine, considered as one of the main players of cancer initiation and progression [8–10]. Owing to this, hybrid 3D biomimetic scaffolds of chemically modified HA have been developed as a liver cancer model [11].…”

“…component comprised of repeated disaccharide units of glucuronic acid and N-acetylglucosamine, considered as one of the main players of cancer initiation and progression [8][9][10]. Owing to this, hybrid 3D biomimetic scaffolds of chemically modified HA have been developed as a liver cancer model [11].…”