MULTIPOTENTIALITY OF SINGLE EMBRYONAL CARCINOMA CELLS.

Summary In order to test the hypothesis that embryonal carcinoma cells are multipotential stem cells of a teratocarcinoma, an in vivo cloning technic was designed. Small embryoid bodies containing mostly embryonal carcinoma were obtained from ascitic conversion of a murine teratocarcinoma and were dissociated with trypsin to form a suspension of single cells; the single cells were picked up in small capillary tubes and transplanted directly into mice. From over 1700 single cell grafts, 44 clonal lines were obtained; 43 of these lines were teratocarcinomas composed of as many as fourteen well differentiated somatic tissues in addition to embryonal carcinoma. These 43 lines varied in their degree of differentiation, capacity to produce embryoid bodies, and in growth rate. The remaining clonal line showed limited potential for differentiation, producing only yolk sac, trophoblast, and embryonal carcinoma. The results demonstrated the multipotentiality of single embryonal carcinoma cells, as well as the heterogeneity of the embryonal carcinoma of a teratocarcinoma. The capacity of single embryonal carcinoma cells to differentiate into benign tissues supports neither the dogma of the irreversibility of the malignant transformation nor the somatic cell mutation theory of cancer. These findings were interpreted as giving strong support to the stem cell theory of cancer.

[1]  G. B. Pierce,et al.  RELATIONSHIP BETWEEN GROWTH RATE AND DIFFERENTIATION OF MELANOMA IN VIVO. , 1964, Journal of the National Cancer Institute.

[2]  W. H. Murphy,et al.  Handbook of cell and organ culture , 1964 .

[3]  M. C. Niu,et al.  Ribonucleic acid-induced changes in mammalian cells. , 1961, Proceedings of the National Academy of Sciences of the United States of America.

[4]  K. Sanford,et al.  Cloning of mammalian cells by a simplified capillary technique. , 1961, Experimental cell research.

[5]  G. B. Pierce,et al.  An ovarian teratocarcinoma as an ascitic tumor. , 1960, Cancer research.

[6]  G. B. Pierce,et al.  Testicular teratomas. II. Teratocarcinoma as an ascitic tumor , 1959, Cancer.

[7]  G. B. Pierce,et al.  Testicular teratomas. I. Demonstration of teratogenesis by metamorphosis of multipotential Cells , 1959, Cancer.

[8]  A. Levan,et al.  Cytologic and functional characterization of single cell clones isolated from the Krebs-2 and Ehrlich ascites tumors. , 1958, Journal of the National Cancer Institute.

[9]  L. C. Stevens Studies on transplantable testicular teratomas of strain 129 mice. , 1958, Journal of the National Cancer Institute.

[10]  T. Puck,et al.  Clonal growth of mammalian cells in vitro; growth characteristics of colonies from single HeLa cells with and without a feeder layer. , 1956 .

[11]  S. Makino FURTHER EVIDENCE FAVORING THE CONCEPT OF THE STEM CELL IN ASCITES TUMORS OF RATS , 1955, Annals of the New York Academy of Sciences.

[12]  R. Dulbecco,et al.  KINETICS OF THE RELEASE OF POLIOMYELITIS VIRUS FROM SINGLE CELLS , 1955, Virology.

[13]  R. Dulbecco,et al.  Kinetics of the release of poliomyelitis virus from single cells. , 1955, Annals of the New York Academy of Sciences.

[14]  S. Makino,et al.  Cytological studies of tumors. XIV. Isolation of single-cell clones from a mixed-cell tumor of the rat. , 1955, Journal of the National Cancer Institute.

[15]  E. Fekete,et al.  Studies on a transplantable teratoma of the mouse. , 1952, Cancer research.

[16]  K. Hosokawa Further research on transplantation of Yoshida sarcoma with single cell and with cell-free tumor ascites. , 1950, Gan.

[17]  D. Fawcett Bilateral ovarian teratomas in a mouse. , 1950, Cancer research.

[18]  石橋 嘉久藏 Studies on the number of cells necessary for the transplantation of Yoshida Sarcoma : 一箇の細胞による腫瘍の移植 , 1949 .

[19]  K. Sanford,et al.  The growth in vitro of single isolated tissue cells. , 1948, Journal of the National Cancer Institute.

[20]  E. B. Jackson,et al.  Studies on a Transplantable Embryoma of the Mouse , 1941 .

[21]  J. Furth,et al.  The Transmission of Leukemia of Mice with a Single Cell , 1937 .