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Coexpression of Cytokeratins Characteristic for Myoepithelial and Luminal Cell Lineages in Rat 13762NF Mammary Adenocarcinoma Tumors and Their Spontaneous Metastases

Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center [R. B. L., S. M. N., G. L. N.], and Department of Cell Biology, Baylor College of Medicine [J. A. J., S. R. G.], Houston, Texas 77030

We used immunohistochemical procedures to study the cellular expression and distribution of cytokeratins (CKs) in rat 13762NF mammary adenocarcinoma cells growing at mammary fat pad sites and at spontaneous lymph node and lung sites. In order to establish CK distribution in normal rat mammary epithelia, immature, resting, and lactating rat mammary glands were probed with a panel of monospecific antibodies that recognize individual CKs. Basal/myoepthelial cells were distinguished by expression of CKs 5 and 14 and coexpression of vimentin from luminal cells, which expressed CKs 8, 18, and 19. Antibody to CK 7 recognized luminal epithelium of immature and resting, but not lactating, mammary glands. Myoepithelial cells of lactating mammary gland were weakly recognized by antibodies to CKs 7 and 19. Tumors formed by cell lines and clones derived from parental 13762NF tumor (MTPa, MTC, MTA, and MTF7) were not recognized by any of the anti-CK antibodies. Only vimentin was expressed in these tumors and their metastases. In tumors and metastases generated from cell lines and clones derived from lymph node (MTLY) and lung metastases (MTLn2 and MTLn3) of the 13762NF tumor we observed heterogeneous CK phenotypes. Expression of CKs 5 and 18 was greatly reduced or lacking, while CK 14 was coexpressed with CKs 7, 8, and 19 with or without vimentin. Tumors from the highly metastatic clone MTLn3 had a dominant cellular phenotype, expressing CKs 7, 8, 14, and 19 and vimentin, a pattern that did not match normal mammary epithelia, whether luminal, basal/myoepithelial, or the dual-phenotype stem cell, in which CKs 5, 8, 14, and 18 were coexpressed. MTLn3 lymph node and lung metastases expressed the same cellular phenotype as the s.c. growing MTLn3 tumor. The results appear to contradict the belief that malignant mammary tumors may be distinguished from benign tumors or hyperplastic growths by the lack of basal/myoepithelial markers.

¹ Present address: Research Laboratories of Schering AG, 1000 Berlin 65, Federal Republic of Germany.

² Present Address: Department of Biochemistry and Molecular Biology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030.

³ Present Address: College of Veterinary Medicine, Texas A & M University, College Station, TX 77843.

⁴ Supported by United States Department of Health and Human Services Grants R01-HD07495 and HD25189 from the National Institute of Child Health and Development.

⁵ To whom requests for reprints should be addressed. Supported by United States Department of Health and Human Services Grant R35-CA44352 from the National Cancer Institute.

Received 10/ 5/89. Accepted 8/14/91.