Abstract:
:Our study demonstrates that synthetic sialyl Lewis X (SLex) as a ligand for selectins and fibronectin-derived RGDS peptide analogue [Ar(DRGDS)3] inhibits lung metastases produced by i.v. co-injection of B16-BL6 melanoma cells. To investigate the inhibitory mechanisms in a living animal, we performed positron-emission tomography (PET) analysis after i.v. injection of [2-18F]2-fluoro-2v-deoxy-D-glucose-labeled tumor cells with or without liposomal SLex or Ar(DRGDS)3. The real-time PET measurement for the first 120 min, started immediately after injection, showed that tumor-cell arrest, i.e., accumulation in the target organ (lung) was remarkably inhibited by liposomal SLex, but not inhibited by Ar(DRGDS)3 or liposomal Me-SLex, which is not recognized by selectins. In contrast, Ar(DRGDS)3 inhibited the invasion of B16-BL6 cells into reconstituted basement membrane (Matrigel) following tumor arrest, whereas SLex- or Me-SLex-entrapped liposomes did not affect tumor invasion. In the metastatic processes containing tumor-cell lodgement and arrest in the target organ followed by extravasation (invasion), SLex resulted in the inhibition of initial arrest of tumor cells, presumably tumor-endothelium interaction, while Ar(DRGDS)3 achieved inhibition of tumor invasion into basement membrane at later steps of the cascade, consequently leading to inhibition of metastasis. Thus, tumor-cell arrest in lungs in the metastatic processes must be precisely and properly controlled by different adhesion molecules at different stages, which are similar to those observed in leukocyte-endothelium interaction.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Saiki I,Koike C,Obata A,Fujii H,Murata J,Kiso M,Hasegawa A,Komazawa H,Tsukada H,Azuma I,Okada S,Oku Ndoi
10.1002/(SICI)1097-0215(19960315)65:6<833::AID-IJCsubject
Has Abstractpub_date
1996-03-15 00:00:00pages
833-9issue
6eissn
0020-7136issn
1097-0215pii
10.1002/(SICI)1097-0215(19960315)65:6<833::AID-IJCjournal_volume
65pub_type
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