Computerized analysis of tumor cell interactions with extracellular matrix proteins, peptides, and endothelial cells under laminar flow
✍ Scribed by Thomas W. Smith; Zhong Yun; David G. Menter; Larry V. McIntire; Garth L. Nicolson
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 1019 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0006-3592
No coin nor oath required. For personal study only.
✦ Synopsis
Arrest and formation of stable adhesive interactions between circulating cells and the endothelium or exposed subendothelial matrix are important processes in many biological situations. We have developed a highly sensitive hydrodynamic assay that utilizes a parallel-plate flow chamber, video microscopy, and digital image processing t o separate and measure the primary arrest and adhesion stabilization of flowing cells. Our data indicate that primary cell contact triggers secondary adhesion stabilization, and the secondary events are likely to be critical to metastasis formation. To study the relationship between tumor cell adhesion stabilization and organ-specific blood-borne metastasis, we investigated the adhesion stabilization of metastatic murine RAW1 17 large-cell lymphoma cells to the extracellular matrix proteins fibronectin and vitronectin, several Arg-Gly-Asp (RGD) containing peptides, and microvascular endothelial cells from the liver or lung. The highly liver metastatic RAW1 17-HI0 subline showed the fastest stabilization t o fibronectin, vitronectin, and RGD peptides. Poorly metastatic RAW1 17-P cells had stabilization times 3-10 times longer than for RAWl17-HI0 cells, while the lung-and liver-metastatic RAW1 17-L17 subline failed to stabilize at all. The adhesion stabilization of the RAW117-HI0 cells to the extracellular matrix proteins and RGD peptides was inhibited by anti+, integrin monoclonal antibodies and RGD peptides. In contrast, the RAW1 17-L17 subline had the shortest stabilization time to unstimulated microvascular endothelial cells of the lung and hepatic sinusoids, followed by RAWl17-HI0 cells and RAW1 17-P cells.
Monoclonal antibodies against the p3 integrin subunit and RGD peptides did not inhibit adhesion stabilization of RAW1 17-HI0 cells to endothelial cells, suggesting that different metastatic variants of large-cell lymphoma cells use differing mechanisms to adhere to organ-specific endothelial cells. @