Functional role of sialyl Lewis X and fibronectin-derived RGDS peptide analogue on tumor-cell arrest in lungs followed by extravasation
| Autor: | Hideo Tsukada, Ikuo Saiki, Jun Murata, Naoto Oku, Hideki Fujii, Shoji Okada, Makoto Kiso, Ichiro Azuma, Hiroyuki Komazawa, Aya Obata, Akira Hasegawa, Chieko Koike |
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| Rok vydání: | 1996 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Integrins Lung Neoplasms Molecular Sequence Data Melanoma Experimental Oligosaccharides Basement Membrane chemistry.chemical_compound Mice medicine Cell Adhesion Animals Neoplasm Invasiveness Amino Acid Sequence Sialyl Lewis X Antigen Basement membrane Matrigel biology Cell adhesion molecule business.industry Melanoma medicine.disease Neoplastic Cells Circulating Extravasation Fibronectins Fibronectin Mice Inbred C57BL Sialyl-Lewis X medicine.anatomical_structure Oncology chemistry Carbohydrate Sequence Liposomes Cancer research biology.protein Selectins Female business Oligopeptides Selectin Tomography Emission-Computed |
| Zdroj: | International journal of cancer. 65(6) |
| ISSN: | 0020-7136 |
| Popis: | Our study demonstrates that synthetic sialyl Lewis X (SLe x ) 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- 18 F]2-fluoro-2-deoxy-D-glucose-labeled tumor cells with or without liposomal SLe x 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 SLe x , but not inhibited by Ar(DRGDS) 3 or liposomal Me-SLe x , 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 SLe x - or Me-SLe x -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), SLe x 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. |
| Databáze: | OpenAIRE |
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