TY - JOUR
T1 - The origin of metastatic heterogeneity in tumors
AU - Fidler, I. J.
AU - Hart, I. R.
N1 - Funding Information:
The source of this cellular diversity may be dependent upon the origin of the tumor. Those neoplasms that have a multicellular origin, for example, some chemically induced tumors [24], may exhibit cellular heterogeneity because they are populated with pro- Accepted 17 November 1980. *Research supported by the National Cancer Institute Contract No. N01-C0-75380 with Litton Bionetics, Inc. ~To whom requests for reprints should be addressed.
PY - 1981/5
Y1 - 1981/5
N2 - These studies were conducted to determine whether the metastatic heterogeneity that is frequently observed in primary neoplasms is a consequence of multicellular transformation or acquired genetic variability. BALB c embryo fibroblasts were infected in vitro with mouse sarcoma virus. Six tumor colonies, each derived from a single transformed cell, were isolated and propagated as individual cell lines. Twenty-four days after virus infection, mice were injected s.c. or i.v. with viable cells harvested from the individual lines. Subcutaneous tumors developed in nearly all of the mice and regressed 30 days after inoculation. In contrast, the production of lung tumor colonies varied significantly among the cell lines. Moreover, the individual lines were found to be heterogeneous. This conclusion is based on results of experiments in which two cell lines exhibiting either a low or high propensity to produce lung tumor colonies were subcloned. Cells from these subclones were injected i.v. into syngeneic mice. The subclones differed significantly among themselves and from the parent culture in their ability to produce lung tumor colonies. We conclude that regardless of whether neoplasms are unicellular or multicellular in origin, they can be heterogeneous and contain subpopulations of cells with different metastatic properties by the time of diagnosis.
AB - These studies were conducted to determine whether the metastatic heterogeneity that is frequently observed in primary neoplasms is a consequence of multicellular transformation or acquired genetic variability. BALB c embryo fibroblasts were infected in vitro with mouse sarcoma virus. Six tumor colonies, each derived from a single transformed cell, were isolated and propagated as individual cell lines. Twenty-four days after virus infection, mice were injected s.c. or i.v. with viable cells harvested from the individual lines. Subcutaneous tumors developed in nearly all of the mice and regressed 30 days after inoculation. In contrast, the production of lung tumor colonies varied significantly among the cell lines. Moreover, the individual lines were found to be heterogeneous. This conclusion is based on results of experiments in which two cell lines exhibiting either a low or high propensity to produce lung tumor colonies were subcloned. Cells from these subclones were injected i.v. into syngeneic mice. The subclones differed significantly among themselves and from the parent culture in their ability to produce lung tumor colonies. We conclude that regardless of whether neoplasms are unicellular or multicellular in origin, they can be heterogeneous and contain subpopulations of cells with different metastatic properties by the time of diagnosis.
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U2 - 10.1016/0014-2964(81)90049-9
DO - 10.1016/0014-2964(81)90049-9
M3 - Article
C2 - 6271554
AN - SCOPUS:0019461726
SN - 0014-2964
VL - 17
SP - 487
EP - 491
JO - European Journal of Cancer (1965)
JF - European Journal of Cancer (1965)
IS - 5
ER -