O peso molecular do ácido hialurónico influência a sua interação com células do cancro gástrico via interação com o recetor CD44

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O peso molecular do ácido hialurónico influência a sua interação com células do cancro gástrico via interação com o recetor CD44

Segunda, 15.07.2019

O ácido hialurónico é um biopolímero que se acumula no ambiente tumoral, em especial à volta das células cancerígenas. Esta acumulação ocorre devido a alterações na síntese e degradação do HA, resultando na formação de cadeias poliméricas de diferentes tamanhos. Neste estudo, mimetizámos este peculiar microambiente tumoral (i.e. ácido hialurónico de diferentes tamanhos) e avaliámos a resposta de células de cancro gástrico. Selecionámos dois tipos de células: AGS, que apresentam uma baixa expressão de CD44 – um recetor específico que reconhece o ácido hialurónico, e MKN45 que apresenta uma sobre-expressão de CD44. Observámos que cadeias longas de ácido hialurónico promovem uma maior motilidade celular, um aumento da expressão de marcadores de invasão, e promovem a formação de agregados celulares nas células que apresentam uma sobre-expressão de CD44, i.e. células MKN45. Os nossos resultados demonstram que, em células com sobre-expressão de CD44, há uma relação entre a agressividade do cancro e o tamanho do ácido hialurónico.

 

Autores e Afiliações:

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.

 

Revista: Scientific Reports

 

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