Molecular weight of surface immobilized hyaluronic acid influences CD44-mediated binding of gastric cancer cells

Abstract

The physiological importance of the interactions between hyaluronic acid (HA) and its main membrane receptor, CD44, in pathological processes, e.g. cancer, is well recognized. However, these interactions are mainly studied in solution, whereas HA in the extracellular matrix (ECM) is partially immobilized via its interactions with other ECM components. We therefore, developed substrates in which HA is presented in an ECM-relevant manner. We immobilized HA with different molecular weights (Mw) in a Layer-by-Layer (LbL) fashion and studied the interactions of the substrates with CD44 and two human gastric cancer cell lines that overexpress this receptor, namely AGS and MKN45. We demonstrate that MKN45 cells are more sensitive to the LbL substrates as compared with AGS. This difference is due to different CD44 expression: while CD44 is detected mainly in the cytoplasm of AGS, MKN45 express CD44 predominantly at the cell membrane where it is involved in the recognition and binding of HA. The invasiveness of the studied cell lines was also evaluated as a function of HA Mw. Invasive profile characterized by low cell adhesion, high cell motility, high expression of cortactin, formation of invadopodia and cell clusters was observed for MKN45 cells when they are in contact with substrates presenting HA of high Mw.

Supramolecular Presentation of Hyaluronan onto Model Surfaces for Studying the Behavior of Cancer Stem Cells

“…On incubation with 1.5 MDa HA, the average roughness in air was measured as 4.59 ± 3.12 nm for the Pep-1-HA surface and 2.96 ± 1.00 nm for the PDL-HA ( Figure 3A,B,E), being consistent with previous values reported for PLL-HA (1.5 MDa) system. [33] In both cases, the average roughness decreased after the deposition of HA ( Figure S7D, Supporting Information).…”

“…[33] HA-patterned surfaces were also fabricated to present HA in discrete regions and study the behavior of colon and breast cancer cells on the HA Adv. For instance, the effect of HA MW on gastric cancer cells was investigated by immobilizing HA through PLL and combining layer-by-layer assembly and crosslinking approaches.…”

Niclosamide encapsulated polymeric nanocarriers for targeted cancer therapy

“…53 Likewise, the high molecular weight of HA used in the study supports in improving the CD44 receptor binding capacity. 54 The quantication cellular internalization analysis performed on MDA-MB-231 cells revealed that [(FITC-PLGA NP)HA] showed more cellular uptake (79.28%) compared to FITC-PLGA NP (43.68%). The results obtained are in coordination with the recent literature.…”

Liposomes Embedded in Layer by Layer Constructs as Simplistic Exosome Transfer Model

“…Mimicking the ECM is a great challenge for tissue engineering because of its high complexity on structural and functional level [27]. Previously, we have shown that layer-by-layer (LbL) approach can be applied to generate reductionist ECM mimics [28,29]. LbL allows assembling nanostructured lms driven by -but not limited to -electrostatic interactions containing polyionic species, including building blocks with potential for biomedical applications [30][31][32].…”

“…LbL allows assembling nanostructured lms driven by -but not limited to -electrostatic interactions containing polyionic species, including building blocks with potential for biomedical applications [30][31][32]. Herein, we assembled ECM mimicking LbL from the polycation poly-Llysine (PLL) and the polyanion hyaluronic acid (HA): PLL is a positively charged polypeptide known to promote cell adhesion, while HA is a negatively charged glycosaminoglycan that is one of the main components of the ECM [28,29,33]. The use of polyions allows us not only to build the LbL but also to immobilize a supported vesicle layer (SVL) of cationic liposomes (Scheme 1).…”