Chemically and virally transformed cells able to grow without anchorage in serum‐free medium: Evidence for an autocrine growth factor

BA 10‐IR transformed cells, obtained by treating Syrian hamster embryo fibroblasts (HEF) with 7‐methylbenz(a)anthracene and cultivated for a long period, are highly tumorigenic and grow in suspension as aggregates (spheroids) (Levy et al., 1976). They also grow in attached form or as spheroids in serumfree (S−) synthetic medium, without insulin and transferrin, and form anchorage‐independent (AI) colonies in this same, but semi‐solid, medium. This exceptional phenotype was acquired stepwise, after other transformation parameters, and appears to be related to the capacity of the transformed cells to respond to a mitogenic growth factor which they secrete. The response to this autocrine factor is amplified by insulin and transferrin. Untransformed HEF, at late and early passages, and also mouse and rat embryo fibroblasts, secrete factors equally active on BA 10‐IR cells; but HEF do not respond, in S− medium, to their factor, or that of BA10‐IR cells. Rat FR3T3 fibroblasts transformed by Kirsten murine sarcoma virus (FR3T3‐Ki cells) also form AI colonies in semi‐solid S− medium, secrete an autocrine factor potentiated by insulin and transferrin, and respond to the factors active on BA10‐IR cells. However, they form far fewer colonies without additives, and respond as well to the mitogenic factors only in the presence of insulin and transferrin.

[1]  D. Lawrence,et al.  Beta-transforming growth factor is stored in human blood platelets as a latent high molecular weight complex. , 1986, Biochemical and biophysical research communications.

[2]  R. Riopelle,et al.  Autonomous proliferation of mewo human melanoma cell lines in serum‐free medium: Secretion of growth‐stimulating activities , 1986, International journal of cancer.

[3]  D. Lawrence,et al.  Conversion of a high molecular weight latent β-TGF from chicken embryo fibroblasts into a low molecular weight active β-TGF under acidic conditions , 1985 .

[4]  D. Lawrence,et al.  Further study of β‐tgfs released by virally transformed and non‐transformed cells , 1985, International journal of cancer.

[5]  D. Lawrence,et al.  Latent beta-transforming growth factor in nontransformed and Kirsten sarcoma virus-transformed normal rat kidney cells, clone 49F. , 1984, Cancer research.

[6]  D. Lawrence,et al.  Normal embryo fibroblasts release transforming growth factors in a latent form , 1984, Journal of cellular physiology.

[7]  C. Heldin,et al.  Growth factors: Mechanism of action and relation to oncogenes , 1984, Cell.

[8]  D. Blakeley,et al.  Transforming growth factors: sources, properties and possible roles in normal and malignant cell growth control. , 1984, Biochemical Society transactions.

[9]  H. Moses,et al.  Comparison of intra- and extracellular transforming growth factors from nontransformed and chemically transformed mouse embryo cells. , 1983, Cancer research.

[10]  D. Mcclure.  Anchorage-independent colony formation of SV40 transformed BALB/c-3T3 cells in serum-free medium: Role of cell- and serum-derived factors , 1983, Cell.

[11]  B. Ozanne,et al.  Polyoma virus-transformed cells produce transforming growth factor(s) and grow in serum-free medium. , 1982, Virology.

[12]  D. Lawrence,et al.  Cells transformed by rous sarcoma virus release transforming growth factors , 1982, Journal of cellular physiology.

[13]  M. Sporn,et al.  Synergistic interaction of two classes of transforming growth factors from murine sarcoma cells. , 1982, Cancer research.

[14]  J. Tooze,et al.  DNA tumor viruses , 1982 .

[15]  David Barnes,et al.  Serum-free cell culture: a unifying approach , 1980, Cell.

[16]  M. Sporn,et al.  Autocrine secretion and malignant transformation of cells. , 1980, The New England journal of medicine.

[17]  B. Ozanne,et al.  Kirsten murine sarcoma virus transformed cell lines and a spontaneously transformed rat cell‐line produce transforming factors , 1980, Journal of cellular physiology.

[18]  G. Todaro,et al.  Transforming growth factors produced by certain human tumor cells: polypeptides that interact with epidermal growth factor receptors. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[19]  I. Fidler,et al.  Correlation of patterns of anchorage-independent growth with in vivo behavior of cells from a murine fibrosarcoma. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Moskowitz,et al.  Growth and G1 arrest of sarcoma virus transformed cells in serum free media , 1979 .

[21]  G. Todaro,et al.  Growth factors from murine sarcoma virus-transformed cells. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Rhim,et al.  Correlation of Cellular Aggregation of Transformed Cells with Their Growth in Soft Agar and Tumorigenic Potential 1 , 1977, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[23]  D. Papadopoulo,et al.  Transformation of hamster embryo cells by 7-methyl benz(a)anthracene in vitro: tumorigenicity, chromosome pattern and spheroid formation. , 1976, European journal of cancer.

[24]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[25]  V. Freedman,et al.  Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[26]  P. Vigier,et al.  Titrage de la tumorigénicité des cellules transformées sur la membrane chorio‐allantoïdienne de l'oeuf de poule , 1969 .

[27]  Anita B. Roberts,et al.  Autocrine growth factors and cancer , 1985, Nature.

[28]  M. Sporn,et al.  Type beta transforming growth factor: a bifunctional regulator of cellular growth. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[29]  D. Lawrence.  Transforming growth factors—an overview , 1985, Biology of the cell.

[30]  B. Ozanne,et al.  Transforming growth factor(s) production enables cells to grow in the absence of serum: an autocrine system. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[31]  H. Hanafusa.  Cell Transformation by RNA Tumor Viruses , 1977 .