Endogenous and exogenous galectin-3 promote the adhesion of tumor cells with low expression of MUC1 to HUVECs through upregulation of N-cadherin and CD44

Abstract

Tumor cell-endothelial adhesion is one of the key steps in tumor cell haematogenous dissemination in metastasis and was previously shown to be mediated by interaction of galectin-3 with the transmembrane mucin protein MUC1. In this study, the effect of exogenous as well as endogenous galectin-3 on adhesion of two cell lines (low MUC1-expressing human prostate cancer PC-3M cells and non-small-cell lung cancer A549 cells) to monolayer of umbilical vein endothelial cells (HUVECs) was investigated. We found that suppression of endogenous galectin-3 expression reduced tumor cell adhesion to HUVECs and also decreased cell invasion and migration. Exogenous galectin-3 promoted tumor cell adhesion to HUVECs by entering cells. Both exogenous and endogenous galectin-3 upregulated the expression of β-catenin and increased β-catenin nuclear accumulation, and subsequently upregulated the expression of N-cadherin and CD44. We deduced that both exogenous as well as endogenous galectin-3 promoted low MUC1-expressing cancer cell adhesion to HUVECs by increasing the expression of N-cadherin and CD44 via an increase of nuclear β-catenin accumulation. These results were confirmed further by using a β-catenin/TCF transcriptional activity inhibitor, N-cadherin or CD44 siRNAs. Taken together, our results suggest a new molecular mechanism of galectin-3-mediated cell adhesion in cancer metastasis.

Galectin‐3 mediates pulmonary vascular endothelial cell dynamics via TRPC1/4 under acute hypoxia

“…However, many other studies have supported the notion that both exogenous and endogenous Gal‐3 carry out the same functions. [ 26,27 ]…”

“…However, many other studies have supported the notion that both exogenous and endogenous Gal-3 carry out the same functions. [26,27] TRPC1 and TRPC4 were selected for this study because they play important roles in the regulation of endothelial function. [28] However, the roles of TRPC1/4 in apoptosis and autophagy have not been elucidated.…”

Effects of 2,2',4'‑trihydroxychalcone on the proliferation, metastasis and apoptosis of A549 human lung cancer cells

“…5B , the expression of N-cadherin and E-selectin was significantly reduced following treatment with different concentrations of 7a. These two adhesion molecules have been proven to be involved in adhesion between tumor cells and HUVECs ( 10 , 15 ). Adhesion could then promote tumor cell aggregation in the blood vessels, which could avoid anoikis and increase the tumor metastasis potential.…”

N-Linked glycosylation profiles of therapeutic induced senescent (TIS) triple negative breast cancer cells (TNBC) and their extracellular vesicle (EV) progeny

“…41 Galectin-3 which is present in higher abundances in TIS cells is known to upregulate CD44 expression. 42 The increased abundance of CD44 on the TIS membrane suggests that it may have a role in TIS cell adhesion. CD44 plays a role in breast cancer cell metabolism with CD44 knockdown in breast cancer cells decreasing glucose uptake, ATP and lactate production.…”