Histomorphologically intact primary human breast lesions and cancers can be propagated in nude mice.
The natural history of various human breast lesions and cancer in patient is difficult to study since diagnosis is established only after surgical ablation and therefore the clinical course of the undisturbed lesion in vivo can no longer be followed. Development of an experimental system which can propagate and maintain human breast lesions and cancer, similar to those seen in surgical breast specimens, may be a first step in the analyses of these various entities. We report that histomorphologically intact human breast lesions and cancer can be recreated in an experimental system using athymic nude mice. When the dissociated cells from surgical breast cancer specimens are embedded in extracellular matrices (collagen gel, Matrigel, or a mixture of the two) and then transplanted into athymic nude mice, the transplanted cells undergo morphogenesis to reflect their original phenotype. A mixture of the two matrices most closely mirrored the breast tissue in situ when stained with Alcian blue-PAS which stains for mucins. In this mixture, not only is the histomorphology recreated, but well-established clinical molecular markers including the estrogen receptor, c-erbB-2 (HER-2/neu), and aberrant cell proliferation are maintained. With the use of an appropriate extracellular matrices, surgical specimens of human breast lesions and cancer can be analyzed in an in vivo experimental system.
Yang
J
J
Cancer Research Laboratory and Department of Molecular and Cell Biology, University of California, 491 LSA, Berkeley, CA 94720, USA. yjason.sf@www.att.net
Guzman
R
R
Nandi
S
S
D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000818:Animals; D001940:Breast / Q000737:chemistry / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D005260:Female; D005782:Gels; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011509:Proteoglycans / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
D000199:Actins; D003094:Collagen; D004338:Drug Combinations; D005782:Gels; D007797:Laminin; D018809:Proliferating Cell Nuclear Antigen; D011509:Proteoglycans; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C059485:matrigel