Involvement of hepatocyte growth factor in increased integrin expression on HepG2 cells triggered by adhesion to endothelial cells

Abstract

Summary Adhesion of cancer cells to vascular endothelium is an important step in haematogenous metastasis of cancer. A human hepatocellular carcinoma cell line, HepG2, strongly adheres to human umbilical vein endothelial cells (HUVECs) through the interaction of Eselectin and its carbohydrate ligand sialyl Lewis X. In this study, we investigated alteration in integrin expression on HepG2 cells, which follows the selectin-mediated initial adhesion of HepG2 cells to HUVECs. Expression of afil integrin was markedly increased when the HepG2 cells adhered to HUVECs. Among the tested cytokines that are known to be produced by endothelial cells, recombinant hepatocyte growth factor (rHGF) could replace the effect of HUVECs, and a similar increase in integrin expression was observed by the addition of 20 ng ml-' rHGF to HepG2. The increment of a2fil integrin expression was significantly inhibited by anti-HGF neutralizing antibody treatment. HepG2 cells expressed a2, a6, f, and 4 integrin subunits, but expression of integrins other than a2fi was not affected by the rHGF treatment.The rHGF treatment of HepG2 cells resulted in augmented adhesion to immobilized collagen. This augmentation in adhesion to collagen was completely blocked by the addition of anti-a2-or anti-,B-integrin antibody. In double-chamber chemoinvasion experiments, transmigration of the HepG2 cells through extracellular matrix (ECM) gel was significantly accelerated by co-cultivation with HUVECs. A similar level of enhancement in transmigration activity of the cancer cells was observed by the addition of rHGF. Our interpretation of the results described above is that the cancer cells received stimulation from cytokines, such as HGF, presented by vascular endothelial cells, following the initial adhesion of cancer cells via selectins. This resulted in the secondary increment in the expression of cell adhesion molecules, such as the a2f, integrin, and led to the augmented adhesive activities of cancer cells towards extracellular matrices at vascular walls. We suggest that this sequence of events is involved in the facilitated migration of some cancer cells to extravascular tissues.

Hypoxia induces adhesion molecules on cancer cells: A missing link between Warburg effect and induction of selectin-ligand carbohydrates

“…Cell-adhesion experiments were performed as described (17)(18)(19). SW480 cells were cultured in monolayer in 24-well plates for 7 days under hypoxic or normoxic conditions.…”

HGF Activates Signal Transduction from EPO Receptor on Human Cord Blood CD34 + /CD45 + Cells

“…HGF is a cytokine with many functions targeting various tissues and organs [1][2][3][4][5][6][7][8]. In the hematopoietic system, Iguchi, Sogo, Hisha et al HGF plays an important role in physiological [16][17][18]20] and pathological states [9][10][11][12][13][14][15].…”

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

“…22-25 (b) In some cells carcinogenesis is associated with a switch in integrin expression; for example, the major integrins a5b1 and a6b1 on normal hepatocytes are replaced by a1b1, a2b1 and a3b1, which are abundantly expressed in cancer cells. [26][27][28] This switch of integrin expression is associated with the acquisition of the migratory capacity, suggesting an important role for these integrins in cancer cell motility. Furthermore, several growth factors, which are abundantly expressed in the tumor microenvironment, are considered potent stimulators of the integrin expression.…”