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Isolation and Characterization of a Highly Malignant Variant of the SW480 Human Colon Cancer Cell Line¹

Comprehensive Cancer Center and Institute of Cancer Research [N. T., W. J., D. W., S. M. K., I. B. W.], and Departments of Pathology [H. H.] and Genetics and Development [D. W., I. B. W.], College of Physicians and Surgeons, Columbia University, New York, New York 10032

³ To whom requests for reprints should be addressed.

We found that the human colon cancer cell line SW480 consists of two distinct subpopulations which we have designated E-type (epithelial) and R-type (round). Pure cultures of each type were obtained by subcloning, and both have maintained their characteristic phenotypes for at least 1 year (40 passages). E-type cells are the major (>98%) type in the parental SW480 cell line. They form flat epithelial-like colonies. In contrast, R-type cells, which constitute a minor fraction (<2%) of the parental cell line, have a rounded shape and grow in clusters of piled-up cells. Compared to E-type cells or the parental SW480 cells, isolated R-type cells display decreased doubling time, loss of contact inhibition, less adhesiveness to culture plates, higher anchorage-independent growth in soft agar, and a much more aneuploid karyotype. When injected s.c. into nude mice, R-type cells produce much larger tumors within the same period of time than E-type cells, and the tumors are less differentiated than those produced by the E-type cells. Cell fusion experiments between R-type and E-type cells revealed that the R-type phenotype is dominant, and the results suggest that this is due to one or a few genetic changes. Taken together, these findings suggest that the R-type cells represent a more malignant variant of the E-type cells. They may be useful, therefore, for studying mechanisms involved in tumor progression.

¹ Supported in part by National Cancer Institute Grant CA021111 and an Award from the Aaron Diamond Foundation.

² Present address: The Second Department of Surgery, Osaka University Medical School, 1-1-50, Fukushima, Fukushima-ku, Osaka 553, Japan.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/10/92. Accepted 10/ 7/92.

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