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American Journal of Pathology, Vol 150, 2099-2112, Copyright © 1997 by American Society for Investigative Pathology

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Early events of metastasis in the microcirculation involve changes in gene expression of cancer cells. Tracking mRNA levels of metastasizing cancer cells in the chick embryo chorioallantoic membrane

T Shioda, LL Munn, MH Fenner, RK Jain and KJ Isselbacher
Laboratory of Tumor Biology, Massachusetts General Hospital Cancer Center, Charlestown 02129-2060, USA.

The early events of metastasis involve multiple interactions between cancer cells and the host microcirculation during cancer cell arrest, adhesion, and extravasation. These interactions may lead to changes in gene expression of the metastasizing cancer cells, although such changes have never been demonstrated directly. To test this hypothesis, B16-F10 murine melanoma cells were injected intravenously into the chick embryo chorioallantoic membrane (CAM), and mRNA levels in the metastasizing cancer cells were evaluated by species-specific reverse transcription polymerase chain reaction. Unlike standard mouse models of experimental metastasis, the CAM model showed successful extravasation of a large number of the arrested cancer cells in the CAM microcirculation without significant cancer cell death, providing a unique opportunity to keep track of mRNA levels in cancer cells during the early phases of metastasis. Using this model, we were able to demonstrate directly the temporal induction of cancer cell genes that potentially affect metastatic efficiency, namely, Fos (5 to 60 minutes after injection), vascular permeability factor (4 to 7 hours), and urokinase plasminogen activator (> 9 hours). In conclusion, using the CAM system, we have observed an alteration of gene expression in cancer cells in the early phases of metastasis, most likely as a consequence of host-cancer cell interactions. These changes may influence the metastatic behavior of cancer cells.

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