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Pattern of Tumor Cell Spread in Tissues and Organs as a Lethal Factor in Tumor-bearing Animals^*

( Laboratory for Experimental Oncology and Department of Surgery, Meharry Medical College, Nashville, Tenn.)

1. Requisite cell numbers of various tumors were inoculated into mice by different routes.

2. Death occurred earliest (average and variation extremes) in the series injected intrapleurally and was attributed to cell infiltration and interstitial tissue thickening in the lung.

3. The short survival span of mice given inoculations intraperitoneally of sarcomas and carcinomas was correlated with the massive infiltration of peritoneal tissue and of abdominal organs by free tumor cells.

4. The earliest death in the series injected subcutaneously was recorded in mice with tumors on the leg and the latest in those with tumors on the back (the amount of proliferated tumor tissue could not be correlated with mortality), which observation suggested as an important lethal factor the compression or obliteration of blood vessels and lymph spaces by spreading tumor growth followed by hemorrhages and atrophic changes. Cells from tumors on the scalp invaded brain tissue and vessels inducing lethal hemorrhages.

5. Unicentric tumor growth, initiated at a single site by a single dose of tumor cells, induced less proliferation and spread of malignant tissue and killed later than pluricentric tumor growth, initiated with ten fractions of the same dose at ten sites.

6. It was concluded that the lethal effect of tumor growth in mice can be interpreted by tracing the pattern of its spread in tissues and organs.

^* This investigation was supported by a grant C-2080 from the National Cancer Institute, N.I.H., U.S. Public Health Service, and a grant-in-aid from the American Cancer Society upon recommendation of the Committee on Growth of the National Research Council.

Received 11/26/54.