Identification of metaplastic variants generated by transfection of a nonmetastatic rat mammary epithelial cell line with DNA from a metastatic rat mammary cell line.
The rat mammary 37 epithelial cell line yields non-metastasizing adenomas in syngeneic rats. On cellular DNA transfection, a series of cell lines have been isolated that grow in drug-selective medium. Representative transfected cell lines all yield tumors in rats that consist predominantly of spindle cells, but two also contain epithelial-like cells and glandlike elements (C18P, C19P). Immunocytochemical staining for milk fat globule membrane antigens, human callus keratin, and laminin confirms the identity of the epithelial cells and suggests a (myo)epithelial origin for the spindle cells. Some of the transfected cell lines also generate well-differentiated metaplastic elements in their tumors. One cell line (CT4-41) produces rhabdomyoblastic and possibly smooth-muscle-related elements; two (C18P, C19P) produce squamous metaplasia and sebaceous elements; and two (CL1-31, C11P) produce cartilaginous elements. The identities of the heterologous elements are confirmed by immunocytochemical staining for myoglobin, actin (CT4-41), keratin (C18P, C19P), type II collagen, and type II keratan sulfate (CL1-31). Those cell lines that have acquired the ability to metastasize from subcutaneous sites (CT4-41, C18P) reproduce the same metaplastic elements in their metastases. Thus, a cloned mammary epithelial cell line can be made to generate many of the well-differentiated, heterologous elements observed in human breast carcinomas, and this change is often associated with the rat cells acquiring metastatic properties.
Cancer and Polio Research Fund Laboratories, Liverpool University, United Kingdom.
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Jamieson
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Rudland
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D002461:Cell Line, Transformed; D004273:DNA, Neoplasm / Q000235:genetics*; D004848:Epithelium / Q000473:pathology; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D008679:Metaplasia; D009362:Neoplasm Metastasis; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling; D014162:Transfection
D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm