Genetic tagging of tumor cells with retrovirus vectors: Clonal analysis of tumor growth and metastasis in vivo
Retrovirus vector infection was used to introduce large numbers of unique genetic markers into tumor cell populations for the purpose of analyzing comparative changes in the clonal composition of metastatic versus that of nonmetastatic tumors during their progressive growth in vivo. The cell lines were SP1, a nonmetastatic, aneuploid mouse mammary adenocarcinoma, and SP1HU9L, a metastatic variant of SP1. Cells were infected with ..delta..e..delta..rhoMoTn, a replication-defective retrovirus vector which possesses the dominant selectable neo gene and crippled long terminal repeats. G418/sup r/ colonies were obtained at a frequency of 4 x 10/sup -3/. Southern blot analysis of a number of clones provided evidence of random and heritable integration of one or two copies of the proviral DNA. Clonal equation of primary tumor growth and the nature of lineage relationships among spontaneous metastases and primary tumors were analyzed by subcutaneously injecting 10/sup 5/ cells from a pooled mixture of 3.6 x 10/sup 2/ G418/sup r/ SP1HU9L or 10/sup 4/ G418/sup r/ SP1 colonies into syngeneic CBA/J mice. The most striking finding was the relative clonal homogeneity of advanced primary tumors; they invariably consisted of a small number (less than 10) of distinct clones despite the fact that hundreds of thousands of uniquely marked clones had been injected.
- Research Organization:
- Divisions of Cancer and Cell Biology and Molecular and Developmental Biology, Mount Sinai Hospital Research Institute, 600 University Avenue, and Dept. of Medical Genetics, Univ. of Toronto, Toronto, Ontario M5G 1X5 (CA)
- OSTI ID:
- 6746378
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 8:8
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CLONE CELLS
ONCOGENIC VIRUSES
MOLECULAR BIOLOGY
TUMOR CELLS
BIOLOGICAL MARKERS
CARCINOMAS
CELL PROLIFERATION
DNA-CLONING
GENETIC MAPPING
IN VITRO
IN VIVO
LUNGS
MAMMARY GLANDS
METASTASES
ANIMAL CELLS
BODY
CELL CULTURES
CLONING
DISEASES
DNA HYBRIDIZATION
GLANDS
HYBRIDIZATION
MAPPING
MICROORGANISMS
NEOPLASMS
ORGANS
PARASITES
RESPIRATORY SYSTEM
VIRUSES
550200* - Biochemistry