Effects of the disintegrin eristostatin on individual steps of hematogenous metastasis
| Autor: | Sahadia Koop, Marsha Grattan, Mary Ann McLane, Vincent L. Morris, Stefan Niewiarowski, E. E. Schmidt, Rama Khokha, Alan C. Groom, Ian C. MacDonald, Ann F. Chambers |
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| Rok vydání: | 1995 |
| Předmět: |
Integrins
Integrin Melanoma Experimental Viper Venoms Metastasis Extracellular matrix Mice Cell Movement Disintegrin medicine Cell Adhesion Animals Neoplasm Metastasis Microscopy Video biology Cell adhesion molecule Melanoma Liver Neoplasms Cell Biology medicine.disease Extravasation Mice Inbred C57BL Immunology Cancer cell biology.protein Cancer research Blood Vessels Peptides |
| Zdroj: | Experimental cell research. 219(2) |
| ISSN: | 0014-4827 |
| Popis: | Adhesion molecules, including integrins, are important for interactions of cancer cells with vessel walls, a step leading to cancer metastasis. Disintegrins block the action of integrins by binding to them. We tested the hypothesis that the disintegrin eristostatin would block metastasis by interfering with cancer cell adhesion to vessel walls, thus preventing extravasation. Experimental metastasis assays, in which B16F1 melanoma cells (controls vs eristostatin-treated, 25 micrograms/ml) were injected via mesenteric veins of anesthetized C57BL/6 mice, showed that eristostatin reduced (P0.05) the mean number of liver metastases from 14.4 to 0.6 at 11 days postinjection (p.i.). We examined three different steps in metastasis at which eristostatin could have exerted its effect, namely, cell arrest, extravasation, and migration. Control and eristostatin-treated B16F1 cells were fluorescently labeled and examined by videomicroscopy in liver microcirculation in vivo at various times up to 14 days p.i. Measurements of vessel size in which cell arrest occurred and length/width ratio of arrested cells showed only small differences between control and eristostatin-treated cells. Eristostatin treatment did not prevent extravasation, and the timing and process of extravasation were similar for both treated and control cells; by 3-4 days p.i. more than 90% of the cells had extravasated or were in the process. Eristostatin also did not affect the ability of extravasated cells to migrate through the extracellular matrix to the subcapsular region where tumors later form. Therefore, we conclude that eristostatin exerted its primary effect by regulating the number of individual cancer cells that grow after extravasation. |
| Databáze: | OpenAIRE |
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