Heterogeneous expression of cytokeratins in metastatic mammary adenocarcinoma cells in vitro and in vivo.

The expression of cytokeratins was investigated in rat 13762NF adenocarcinoma cell lines and clones growing in vitro and in vivo. The anti-cytokeratin monoclonal antibody PKK1 used in this study recognized one cytokeratin with a molecular weight of 54,000 in these cells. Immunofluorescence staining of cultured tumor cells with PKK1 detected cytokeratins in less than 1% of the tumor cells isolated from the locally growing parental tumors, but intense cytokeratin staining in the form of fibrils and networks was found in the cell cultures derived from spontaneous metastases. There were variable degrees of staining with the anti-cytokeratin antibody in cultured cells from metastases, indicating phenotypic diversity in the expression of cytokeratins. Staining with PKK1 of frozen sections from locally growing tumors obtained after injecting the cells into the mammary fat pads of syngeneic rats also demonstrated considerable heterogeneity in cytokeratin expression. The anti-cytokeratin reagent stained only a few, isolated cells in frozen sections of tumors established from parental tumor cells, while this reagent stained intensely cells in local tumors and their metastases established from tumor cells cultured from spontaneous lymph node or lung metastases.