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Pathogenesis of Tumor Invasion

II. Aggregate Replication^{* ,}

Joseph Leighton, Richard L. Kalla, James M. Turner, Jr. and Robert H. Fennell, Jr.

( Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh 13, Pennsylvania)

Invasive carcinoma commonly presents a picture of nests of neoplastic cells in a matrix of connective tissue. As the tumor grows and involves larger volumes of tissue, increasing numbers of aggregates of carcinoma cells are seen. Evidently, mechanisms exist by which nests of cells give rise to other nests. Factors within the aggregates as well as factors in the supporting stroma can be expected to play a role in the propagation of aggregates.

In this study, aggregate formation was observed in vitro in the complete absence of living stromal cells. Several cell lines in sponge-matrix tissue culture grew as increasing numbers of multicellular groups. Derivatives of Strain D (obtained originally from infant's foreskin) were studied in detail in several plasma clot systems and in umbilical cord matrix.

When D-189 cells were suspended in a thin plasma clot under agar, enlarging spherical colonies gave rise to ribbons of cells growing on the plasma-glass interface. As primary ribbons lengthened, secondary ribbons appeared in geometric, branching patterns. The final pattern was one of an elaborate criss-cross of many ribbons of cells. In addition to the criss-cross pattern at the plasma-glass interface, when a second plasma clot was used as the overlay, branching cords of cells grew from the initial clump into the substance of the clot. Many globular groups of cells appeared among the branching cords. When the same line was grown in umbilical cord matrix, branching cords of cells produced a complex arborization.

The geometric patterns obtained do not appear to result primarily from cells following preformed mechanical lines provided by the matrix. Instead, the patterns suggest that groups of cells function as integrated units in the propagation of similar groups and that their reproduction may have qualities of predictability and rhythmic periodicity.

^* Presented in part at the joint symposium, "Recent Contributions of Tissue Culture to Cancer Research," of the American Association for Cancer Research and the Tissue Culture Association in Philadelphia, April 11, 1958.

This is publication No. 230 of the Department of Pathology, University of Pittsburgh School of Medicine. The study was supported by Research Grant C-2800 from the National Institutes of Health, Public Health Service.

Medical Student Research Trainee at the University of Pittsburgh, supported by the National Institutes of Health, Public Health Service.

Received 12/14/59.