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Early Cell Motility Changes Associated with an Increase in Metastatic Ability in Rat Prostatic Cancer Cells Transfected with the v-Harvey-ras Oncogene¹

Departments of Urology [A. W. P., J. T. I., B. T., D. S. C. and [A. W. P., D. S. C., [J. T. I., D. S. C.], Pharmacology, and The Oncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

The development of metastatic ability by cancer cells is a multifactorial process whose temporal events are complex and poorly understood. One step in the metastatic process may involve cell motility. Previous studies reported correlations between motility and metastatic ability. Whether this correlation, seen in cancer cells maintained for long periods of time, is an epiphenomenon developing late in the growth of the cancer as a selection artifact of continuous passage, or is critically required for the acquisition of metastatic ability is unknown.

To investigate the relationship between cell motility and the acquisition of metastatic ability, advantage was taken of recently developed DNA transfection methods for inducing high metastatic ability in initially low metastatic cancer cells. The Dunning AT2.1 cell line, a clonal rat prostatic cancer cell line with low metastatic ability, was transfected with a plasmid containing the neomycin resistance gene alone or in combination with the v-Harvey-ras oncogene. A series of the transfected cells was isolated by limiting dilution. After the first in vitro passage following transfection, cells were inoculated into rats to characterize their metastatic ability. The same transfectants were simultaneously studied using our visual grading system of cell motility to study the early motility changes associated with newly acquired metastatic ability. The data demonstrate increased membrane ruffling, pseudopodal extensions and cell translation (translocation) in the v-H-ras-transfected cell lines with high metastatic potential.

¹ This work was supported by Grant CA15416 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Department of Urology, The Johns Hopkins Hospital, Baltimore, MD 21205.

Received 4/21/88. Revised 7/29/88. Accepted 8/ 3/88.