Studies of mammary carcinoma metastasis in a mouse model system. I: Derivation and characterization of cells with different metastatic properties during tumour progression in vivo

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Abstract
The biological and metastatic properties of cells from a murine mammary adenocarcinoma, MTI, were studied during serial transplantation in syngeneic hosts. Over 35 generations the tumour progressed from a well-differentiated, poorly metastatic neoplasm to an anaplastic highly metastatic state. At early passages the tumour yielded uniform cultures of cuboidal epithelial cells, at passage 17 both epithelioid and spindle type cells were present, and by passage 30 only spindle type cells were obtained. Epithelioid cell lines and clones when injected intravenously into syngeneic hosts produced lung colonies only, whereas spindle cell lines were capable of extensive extrapulmonary colonisation. Similar patterns of dissemination and growth were seen in spontaneous metastasis assays. In spite of the marked phenotypic differences in these ‘subpopulations’, their comparable ultrastructural features, oestrogen receptor levels, expression of MMTV antigens, DNA content and lectin binding profiles suggested a common cell lineage. It is proposed that these cell lines will be of use in the determination of tumour and host factors influencing tumour progression and the evolution of metastatic potential.