Development and characterization of breast carcinoma cell lines as in vitro and in vivo models for breast cancer diagnosis and therapy.
To establish a model system for preclinical radioimmunotherapy studies, attempts were made to graft 16 different human breast carcinoma cell lines into BALB/c nu/nu(nude) mice. Nine produced serially transplantable tumors growing at a variable rate, whereas seven failed to do so. Conversely, three new cell lines were established in monolayer culture from transplantable human breast tumors in nude mice. Twelve selected tumors and their corresponding cell lines were characterized for DNA ploidy, % S-phase, and breast epithelial mucin expression by immunohistochemistry and flow cytometry. A wide diversity of these cellular characteristics were found in that each tumor was unique and distinct from the others. DNA ploidy differed among the tumors but was not affected by switching between in vitro to in vivo growth. Some tumors expressed similar levels of the breast mucin both in vitro and in vivo, whereas most expressed lower levels as transplantable tumors. There was a good correlation between immunohistochemical and flow cytometric determination of surface and cytoplasmic mucin expression, and with both techniques estrogen and progesterone receptor positive tumors had significantly higher levels of mucin expression than receptor negative tumors. These 12 transplantable breast tumors, with their corresponding cell lines, provide an excellent model system for testing radioimmunotherapy and other therapeutic reagents because they exhibit diverse phenotypic characteristics that represented a mini-population of breast cancer patients' tumors, allowing assessment of the effect of therapy when confronted with different breast tumors' genotype and phenotype.
Ceriani
R L
RL
John Muir Cancer and Aging Research Institute, Walnut Creek, California 94596.
Peterson
J A
JA
Blank
E W
EW
Chan
C M
CM
Cailleau
R
R
D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000532:radiotherapy*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009077:Mucins / Q000032:analysis; D010641:Phenotype; D011003:Ploidies; D011863:Radioimmunoassay; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure
D004273:DNA, Neoplasm; D009077:Mucins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone