Altered melanoma cell surface glycosylation mediates organ specific adhesion and metastasis via lectin receptors on the lung vascular endothelium

Abstract

Adhesive interactions between the molecules on cancer cells and the target organ are one of the key determinants of the organ specific metastasis. In this communication we show that b1,6 branched N-oligosaccharides which are expressed in a metastasis-dependent manner on B16-melanoma metastatic cell lines, participate in the adhesion process. We demonstrate that high metastatic cells show significantly increased translocation of one of the major carriers of these oligosaccharides, lysosome associated membrane protein (LAMP1), to the cell surface. LAMP1 on high metastatic cells, carry very high levels of these oligosaccharides, which are further substituted with poly N-acetyl lactosamine (polylacNAc), resulting in the expression of high density of very high affinity ligands for galectin-3 on the cell surface. We show that galectin-3 is expressed in highest amount in the lungs as compared to other representative organs. Blocking galectin-3 by pre-incubating the frozen sections of the lungs with 100 mM lactose, substantially inhibited the adhesion of high metastatic cells, while pre-incubation with sucrose had no effect. Finally, by in situ labeling and immunoprecipitation experiment, we demonstrated that the lung vascular endothelial cells express galectin-3 constitutively on their surface. Galectin-3 on the organ endothelium could thus serve as the first anchor for the circulating cancer cells, expressing high density of very high affinity ligands on their surface, and facilitate organ specific metastasis.

C4.4A as a candidate marker in the diagnosis of colorectal cancer

“…Whether, indeed, differences in the C4.4A glycosylation state account for the distorted interaction with galectin-3 remain to be elucidated. However, altered glycosylation in cancer can play an important role in tumour cell adhesion and migration (Orntoft and Vestergaard, 1999), as well as in extravasation via interaction with galectin-3 on endothelial cells (Lehr and Pienta, 1998;Glinsky et al, 2000;Krishnan et al, 2005). Two additional membrane proteins that associate with C4.4A in HaCaT cells, but very rarely in tumour cells as well as a high molecular weight protein, mainly detected in MCF-7 cells, remain to be identified.…”

Glycobiology of fertilization in the pig

“…The major GNA-binding proteins of the OAMF, LAMP-1 and 2 as well as ORP150, however, are not listed. LAMP-1 and LAMP-2 constitute the main glycoprotein components of the lysosomal membranes (Fukuda et al, 1991) and have also been detected at the extracellular surface of various cells (Chang et al, 2004;Krishnan et al, 2005) and as a soluble form of LAMP-1 (Chang et al, 2004). LAMP-1 found in the oviductal fluid may therefore also present the soluble form, which has lost the membrane anchor and the small cytoplasmatic domain.…”

MTSS1 is a metastasis driver in a subset of human melanomas

“…2a). Two of these genes have an already proposed or documented role in melanoma cell biology with SHC1 acting on RAS signalling 22 and LAMP1 being implicated in melanoma metastasis 23 , thus supporting the potential biological significance of the applied selection approach. As we were particularly interested in the identification of drivers of the disease and, in contrast to SSR2-an endoplasmic reticulum translocon component 24 , MTSS1's property (MIM, KIAA0429) to regulate actin and plasma membrane dynamics via interaction with actin 25,26 provided a potential link to the phenotype in the invasion assay screen, we decided to study the contribution of MTSS1 to melanoma cell biology in more detail.…”