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Expression of Myoepithelial Markers in Mammary Carcinomas of 119 Pet Rabbits.

ABSTRACT: Most mammary tumors in pet rabbits are carcinomas; prognostic factors are unknown. The aim of this study on rabbit mammary carcinomas was to determine the expression of myoepithelial markers that have a prognostic relevance in human cancers. Mammary carcinomas (n = 119) of female or female-spayed pet rabbits were immunostained for cytokeratin AE1/AE3, vimentin, smooth muscle actin (SMA), and calponin; and percentages of non-neoplastic myoepithelial cells (ME cells) and calponin-positive neoplastic cells were determined. Using statistical analysis, data were correlated with the age of the rabbits and histological tumor characteristics. All carcinomas contained retained spindle-shaped ME, while 115 also contained hypertrophic ME (HME). A statistically significant relationship existed between a higher age and an increase in HME. In 111 carcinomas (93%), tumor cells expressed calponin. There was a significant correlation between higher percentages of calponin-positive tumor cells and a lower mitotic count, an increased percentage of tubular growth, and a lower grading score, respectively. Data suggest that pet rabbit mammary carcinomas develop from progression of in situ cancer and that the extent of calponin expression in tumor cells influences their biological behavior. These results provide the basis for a long-term follow-up on the prognostic significance of calponin expression in mammary cancer cells.

SUBMITTER: Degner S

PROVIDER: S-EPMC6826665 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Expression of Myoepithelial Markers in Mammary Carcinomas of 119 Pet Rabbits.

Degner Sophie S Schoon Heinz-Adolf HA Degner Sebastian S Baudis Mathias M Schandelmaier Claudia C Aupperle-Lellbach Heike H Schöniger Sandra S

Animals : an open access journal from MDPI 20190928 10

Most mammary tumors in pet rabbits are carcinomas; prognostic factors are unknown. The aim of this study on rabbit mammary carcinomas was to determine the expression of myoepithelial markers that have a prognostic relevance in human cancers. Mammary carcinomas (<i>n</i> = 119) of female or female-spayed pet rabbits were immunostained for cytokeratin AE1/AE3, vimentin, smooth muscle actin (SMA), and calponin; and percentages of non-neoplastic myoepithelial cells (ME cells) and calponin-positive n ...[more]

PMID: 31569405

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Project description:Intercellular communication is essential for glandular functions and tissue homeostasis. Gap junctions couple cells homotypically and heterotypically and co-ordinate reciprocal responses between the different cell types. Connexins (Cxs) are the main mammalian gap junction proteins, and the distribution of some Cx subtypes in the heterotypic gap junctions is not symmetrical; in the murine mammary gland, Cx26, Cx30 and Cx32 are expressed only in the luminal epithelial cells and Cx43 is expressed only in myoepithelial cells. Expression of all four Cxs peaks during late pregnancy and throughout lactation suggesting essential roles for these proteins in the functional secretory activity of the gland. Transgenic (Tg) mice over-expressing Cx26 driven by keratin 5 promoter had an unexpected mammary phenotype: the mothers were unable to feed their pups to weaning age leading to litter starvation and demise in early to mid-lactation. The mammary gland of K5-Cx26 female mice developed normally and produced normal levels of milk protein, suggesting a defect in delivery rather than milk production. Because the mammary gland of K5-Cx26 mothers contained excessive milk, we hypothesized that the defect may be in an inability to eject the milk. Using ex vivo three-dimensional mammary organoid cultures, we showed that tissues isolated from wild-type FVB females contracted upon treatment with oxytocin, whereas, organoids from Tg mice failed to do so. Unexpectedly, we found that ectopic expression of Cx26 in myoepithelial cells altered the expression of endogenous Cx43 resulting in impaired gap junction communication, demonstrated by defective dye coupling in mammary epithelial cells of Tg mice. Inhibition of gap junction communication or knock-down of Cx43 in organoids from wild-type mice impaired contraction in response to oxytocin, recapitulating the observations from the mammary glands of Tg mice. We conclude that Cx26 acts as a trans-dominant negative for Cx43 function in myoepithelial cells, highlighting the importance of cell type-specific expression of Cxs for optimal contractile function of the mammary myoepithelium.

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Expression of Myoepithelial Markers in Mammary Carcinomas of 119 Pet Rabbits.

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Expression of Myoepithelial Markers in Mammary Carcinomas of 119 Pet Rabbits.

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