Molecular weight of hyaluronic acid influences its interaction with gastric cancer cells through the CD44 receptor

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Molecular weight of hyaluronic acid influences its interaction with gastric cancer cells through the CD44 receptor

Monday, 15.07.2019

Hyaluronic acid or hyaluronan is a biopolymer that accumulates in tumor microenvironments and around cancer cells. The accumulation is concomitant with changes of hyaluronan properties resulting in the generation of chains with different sizes. In this study, we mimic this peculiar tumor microenvironment and studied the response of gastric cancer cells. We selected two types of cells: AGS that have low expression of CD44 – a specific cellular receptor that recognize the hyaluronan and MKN45 with high CD44 expression. We observed that long hyaluronan chains cause high cellular motility, increased expression of invasive markers, and promote cell aggregations for CD44-expressing cells, i.e. MKN45 cells. Our results demonstrate a relationship between cancer aggressiveness and the size of hayluronan for cells with high expression of CD44.

 

Authors and Affiliations:

Sara Amorim (3B’s Research Group, I3Bs – Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães, Portugal; ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal. The Discoveries Centre for Regenerative and Precision Medicine, Guimarães, Portugal)

Diana Soares da Costa (3B’s Research Group, I3Bs – Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães, Portugal; ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal.)

Daniela Freitas (IPATIMUP/i3S, Universidade do Porto, Porto; ICBAS, Porto)

Celso A. Reis (IPATIMUP/i3S, Universidade do Porto, Porto; ICBAS, Porto; Faculdade Medicina, Porto)

Rui L. Reis (3B’s Research Group, I3Bs – Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães, Portugal; ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal. The Discoveries Centre for Regenerative and Precision Medicine, Guimarães, Portugal)

Iva Pashkuleva (3B’s Research Group, I3Bs – Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães, Portugal; ICVS/3B’s - PT Government Associate Laboratory, Braga/, Portugal.)

Ricardo A. Pires (3B’s Research Group, I3Bs – Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Guimarães, Portugal; ICVS/3B’s - PT Government Associate Laboratory, Braga/, Portugal. The Discoveries Centre for Regenerative and Precision Medicine, Guimarães, Portugal)

 

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.

 

Journal: Scientific Reports

 

Link: https://www.nature.com/articles/s41598-018-34445-0