Gennari, Arianna

Rosa, J. M. Rios de La

Ríos De la rosa, Julio Manuel

Tirella, A.

Tirelli, N.

CD44 is the major cell surface receptor of hyaluronic acid (HA) and mediates the response of cells to their cellular microenvironment. Whereas the standard isoform (CD44s) is ubiquitously expressed throughout the body, variant isoforms (CD44v) are aberrantly overexpressed in certain tumours and integrate signaling in (pre)metastatic niches, thus CD44 has become a potential target for cancer chemotherapy. However, CD44 is also one of the most abundantly expressed macrophage receptors, rendering this cellular type a competitor for the uptake of targeted nanocarriers in vivo. In this study, we have established an in vitro human macrophage model, which would allow the off-targeting effects to be determined. In particular, we have developed a standard procedure for THP-1 (human monocytic leukaemia cell line) monocyte-to-macrophage differentiation by using phorbol 12-myristate 13-acetate (PMA), characterising the resulting phenotype. The successfully differentiated THP-1 monocytes showed a significantly increased expression of CD44, which was compared in terms of a) amount and isoform composition, b) internalisation kinetics of CD44-binding nanoparticles to that of a tumoural cell line (HT-29)

Characterisation of THP-1 macrophages as an in vitro model for CD44-targeted therapies

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