Mannose receptor-mediated endothelial cell activation contributes to B16 melanoma cell adhesion and metastasis in liver

✍ Scribed by Lorea Mendoza; Elvira Olaso; Miren J. Anasagasti; Angela M. Fuentes; Fernando Vidal-Vanaclocha

• Book ID: 101258711
• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 243 KB
• Volume: 174
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/(sici)1097-4652(199803)174:3<322::aid-jcp6>3.0.co;2-q

✦ Synopsis

The role of mannose receptors from hepatic sinusoidal endothelium (HSE) in liver colonization by B16 melanoma (B16M) cells was studied. The expression of high mannose-type oligosaccharides on the surface of B16M cells was enhanced by in vitro treatment with 1-deoximannojirimycin (1-DMM). There was a significant (P õ 0.01) enhancement of hepatic metastasis when B16M cells were 1-DMMtreated before being intrasplenically injected into C57BL/6J mice. Intraperitoneal administration of 5 mg/kg recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) inhibited the 1-DMM-induced enhancement of metastasis. Expression of high mannose-type oligosaccharides on the surface of 1-DMM-treated B16M cells and their in vitro adhesion to the HSE was significantly correlated (R Å 0.82). The addition of either 100 mg/ml mannan or paraformaldehyde (PFA)fixed 1-DMM-treated B16M cells to cultured HSE for a period of 12 h significantly (P õ 0.01) increased the release of IL-1b from the HSE compared to that liberated by the HSE incubated with either basal medium or PFA-fixed untreated B16M cells. The same HSE treatments also significantly (P õ 0.01) increased the degree of adhesion of other B16M cells to HSE, being abrogated by anti-mouse vascular cell adhesion molecule-1 (VCAM-1) antibodies. The conditioned media from HSE cultures, activated by PFA-fixed, 1-DMM-treated B16M cells significantly (P õ 0.01) increased B16M cell proliferation when compared to conditioned media from HSE cultures incubated with PFA-fixed, untreated B16M cells. Thus, 1-DMM treatment of B16M cells enhanced the development of hepatic metastasis by IL-1-dependent mechanisms. The mechanism is consistent with in vitro mannose receptor-mediated melanoma cell attachment to the HSE, which subsequently upregulates IL-1b release, VCAM-1-dependent adherence, and melanoma growth factor(s) release by HSE.