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Bovine Mammary Progenitor Cells: Current Concepts and Future Directions

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Abstract

Although cell number is positively correlated with milk production, much remains to be learned about the bovine mammary stem cell and progenitor cells. Bovine mammary development is driven by many of the same classic mammogenic hormones studied in murine models, yet histologic features of bovine mammary development differ from that of rodent models. Most notably, terminal end buds, as they have been described for murine models, do not exist in the bovine mammary gland. However, among the most important common features of mammary development in disparate species is the involvement of histologically distinct, lightly staining epithelial cells as putative stem and progenitor cells. Although stem cell research has often focused on mammary development, mammary stem cells seemingly provide the basis for mammary growth and cell turnover in the mature animal. These cells provide an obvious focus for research aimed at increasing the efficiency of milk production. This review addresses recent findings concerning the histology and molecular physiology of putative bovine mammary stem and progenitor cell populations, areas where more study is critically needed, and areas where studies of bovine mammary physiology may present a unique opportunity to better understand mammary physiology in many species.

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Abbreviations

BrdU:

bromodeoxyuridine

bST:

bovine somatotropin

ERá:

estrogen receptor-alpha

ERâ:

estrogen receptor-beta

TEB:

terminal end bud

TDU:

terminal ductal unit

References

  1. Capuco AV, Ellis S, Wood DL, Akers RM, Garrett W. Postnatal mammary ductal growth: Three-dimensional imaging of cell proliferation, effects of estrogen treatment and expression of steroid receptors in prepubertal calves. Tissue Cell 2002;34:9–20.

    Article  Google Scholar 

  2. Ellis S, Capuco AV. Cell proliferation in bovine mammary epithelium: Identification of the primary proliferative cell population. Tissue Cell 2002;34:21–8.

    Article  Google Scholar 

  3. Humphreys RC, Krajewska M, Krnacik S, Jaeger R, Weiher H, Krajewski S, Reed JC, Rosen JM. Apoptosis in the terminal endbud of the murine mammary gland: A mechanism of ductal morphogenesis. Development 1996;122:4013–22.

    CAS  PubMed  Google Scholar 

  4. Anderson RR, Harness JR, Snead AF, Salah MS. Mammary growth pattern in goats during pregnancy and lactation. J Dairy Sci 1981;64:427–32.

    CAS  PubMed  Google Scholar 

  5. Capuco AV, Wood DL, Baldwin R, McLeod K, Paape MJ. Mammary cell number, proliferation, and apoptosis during a bovine lactation: Relation to milk production and effect of bST. J Dairy Sci 2001;84:2177–87.

    CAS  PubMed  Google Scholar 

  6. Capuco AV, Li M, Long E, Ren S, Hruska KS, Schorr K, Furth PA. Concurrent pregnancy retards mammary involution: Effects on apoptosis and proliferation of the mammary epithelium after forced weaning of mice. Biol Reprod 2002;66:1471–76.

    CAS  PubMed  Google Scholar 

  7. Capuco AV, Akers RM. Mammary involution in dairy animals. J Mammary Gland Biol Neoplasia 1999;4:137–44.

    Article  CAS  PubMed  Google Scholar 

  8. Jones PH, Watt FM. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 1993;73:713–24.

    Article  CAS  PubMed  Google Scholar 

  9. Cosentino L, Shaver-Walker P, Heddle JA. The relationships among stem cells, crypts, and villi in the small intestine of mice as determined by mutation tagging. Dev Dyn 1996;207:420–8.

    Article  CAS  PubMed  Google Scholar 

  10. Fliedner TM. The role of blood stem cells in hematopoietic cell renewal. Stem Cells 1998;16(Suppl 1):13–29.

    PubMed  Google Scholar 

  11. Chepko G, Smith GH. Mammary epithelial stem cells: Our current understanding. J Mammary Gland Biol Neoplasia 1999;4:35–52.

    Article  CAS  PubMed  Google Scholar 

  12. Chepko G, Smith GH. Three division-competent, structurally-distinct cell populations contribute to murine mammary epithelial renewal. Tissue Cell 1997;29:239–53.

    CAS  PubMed  Google Scholar 

  13. Smith GH, Medina D. A morphologically distinct candidate for an epithelial stem cell in mouse mammary gland. J Cell Sci 1988;90:173–84.

    PubMed  Google Scholar 

  14. Ferguson DJ. Ultrastructural characterisation of the proliferative (stem?) cells within the parenchyma of the normal “resting” breast. Virchows Arch A Pathol Anat Histopathol 1985;407:379–85.

    Article  CAS  PubMed  Google Scholar 

  15. Joshi K, Ellis JTB, Hughes CM, Monaghan P, Neville AM. Cellular proliferation in the rat mammary gland during pregnancy and lactation. Lab Invest 1986;54:52–61.

    CAS  PubMed  Google Scholar 

  16. Ellis S, Edwards FG, Akers RM. Morphological and histological analysis of the prepubertal ovine mammary gland. J Dairy Sci 1995;78(Suppl. 1):157.

    Google Scholar 

  17. Li P, Wilde CJ, Finch LM, Fernig DG, Rudland PS. Identification of cell types in the developing goat mammary gland. Histochem J 1999;31:379–93.

    Article  CAS  PubMed  Google Scholar 

  18. Nickerson SC, Akers RM, Weinland BT. Cytoplasmic organization and quantitation of microtubules in bovine mammary epithelial cells during lactation and involution. Cell Tissue Res 1982;223:421–30.

    Article  CAS  PubMed  Google Scholar 

  19. Cheng G, Weihua Z, Warner M, Gustafsson JA. Estrogen receptors ER alpha and ER beta in proliferation in the rodent mammary gland. Proc Natl Acad Sci U S A 2004;101:3739–46.

    Article  CAS  PubMed  Google Scholar 

  20. Schams D, Kohlenberg S, Amselgruber W, Berisha B, Pfaffl MW, Sinowatz F. Expression and localisation of oestrogen and progesterone receptors in the bovine mammary gland during development, function and involution. J Endocrinol 2003;177:305–17.

    Article  CAS  PubMed  Google Scholar 

  21. Berry SDK, Jobst PM, Ellis SE, Howard RD, Capuco AV, Akers RM. Mammary epithelial proliferation and estrogen receptor alpha expression in prepubertal heifers: Effects of ovariectomy and growth hormone. J Dairy Sci 2003;86:2098–105.

    CAS  PubMed  Google Scholar 

  22. Anderson E, Clarke RB, Howell A. Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia 1998;3:23–35.

    Article  CAS  PubMed  Google Scholar 

  23. Russo J, Ao X, Grill C, Russo IH. Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res Treat 1999;53:217–27.

    Article  CAS  PubMed  Google Scholar 

  24. Shyamala G. Roles of estrogen and progesterone in normal mammary gland development - Insights from progesterone receptor null mutant mice and in situ localization of receptor. Trends Endocrinol Metab 1997;8:34–9.

    Article  CAS  Google Scholar 

  25. Haslam SZ, Levely ML. Estrogen responsiveness of normal mouse mammary cells in primary cell culture: Association of mammary fibroblasts with estrogenic regulation of progesterone receptors. Endocrinology 1985;116:1835–44.

    CAS  PubMed  Google Scholar 

  26. Zeps N, Dawkins HJ, Papadimitriou JM, Redmond SL, Walters MI. Detection of a population of long-lived cells in mammary epithelium of the mouse. Cell Tissue Res 1996;286:525–36.

    CAS  PubMed  Google Scholar 

  27. Dontu G, Al-Hajj M, Abdallah WM, Clarke MF, Wicha MS. Stem cells in normal breast development and breast cancer. Cell Prolif 2003;36(Suppl 1):59–72.

    Article  CAS  Google Scholar 

  28. Clarke RB, Anderson E, Howell A, Potten CS. Regulation of human breast epithelial stem cells. Cell Prolif 2003;36(Suppl 1):45–58.

    Article  CAS  Google Scholar 

  29. Dontu G, El-Ashry D, Wicha MS. Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol Metab 2004;15:193–97.

    Article  CAS  PubMed  Google Scholar 

  30. Ford TS, Ross MW, Acland HM, Madison JB. Primary teat neoplasia in two yearling heifers. J Am Vet Med Assoc 1989;195:238–39.

    CAS  PubMed  Google Scholar 

  31. Petrites-Murphy MB. Mammary carcinoma with peritoneal metastasis in a cow. Vet Pathol 1992;29:552–53.

    CAS  PubMed  Google Scholar 

  32. Acland HM, Gillette DM. Mammary carcinoma in a mare. Vet Pathol 1982;19:93–95.

    CAS  PubMed  Google Scholar 

  33. Foreman JH, Weidner JP, Parry BW, Hargis A. Pleural effusion secondary to thoracic metastatic mammary adenocarcinoma in a mare. J Am Vet Med Assoc 1990;197:1193–95.

    CAS  PubMed  Google Scholar 

  34. Kato M, Higuchi T, Hata H, Ishikawa Y, Kadota K. Lactalbumin-positive mammary carcinoma in a mare. Equine Vet J 1998;30:358–60.

    CAS  PubMed  Google Scholar 

  35. Rudas P, Bartha T, Toth J, Frenyo VI. Impaired local deiodination of thyroxine to triiodothyronine in dogs with symmetrical truncal alopecia. Vet Res Commun 1994;18:175–82.

    CAS  PubMed  Google Scholar 

  36. Chiedozi LC. Breast cancer in Nigeria. Cancer 1985;55:653–57.

    CAS  PubMed  Google Scholar 

  37. Donegan WL. Mammary carcinoma and pregnancy. Major Probl Clin Surg 1979;5:448–63.

    CAS  PubMed  Google Scholar 

  38. Kuerer HM, Cunningham JD, Brower ST, Tartter PI. Breast carcinoma associated with pregnancy and lactation. Surg Oncol 1997;6:93–98.

    CAS  PubMed  Google Scholar 

  39. Swett WW, Matthews CA, Graves RR. Extreme rarity of cancer in the cow’s udder: A negative finding of vital interest to the dairy industry and to the consumer. J. Dairy Sci. 1940;23:437–46.

    Google Scholar 

  40. Feldman WH. Neoplasms in domesticated animals. Philadelphia and London: W.B. Saunders Co., 1932.

    Google Scholar 

  41. Heerdt BG, Houston MA, Anthony GM, Augenlicht LH. Initiation of growth arrest and apoptosis of MCF-7 mammary carcinoma cells by tributyrin, a triglyceride analogue of the short-chain fatty acid butyrate, is associated with mitochondrial activity. Cancer Res 1999;59:1584–91.

    CAS  PubMed  Google Scholar 

  42. Gaschott T, Maassen CU, Stein J. Tributyrin, a butyrate precursor, impairs growth and induces apoptosis and differentiation in pancreatic cancer cells. Anticancer Res 2001;21:2815–19.

    CAS  PubMed  Google Scholar 

  43. Belobrajdic DP, McIntosh GH. Dietary butyrate inhibits NMU-induced mammary cancer in rats. Nutr Cancer 2000;36:217–23.

    CAS  PubMed  Google Scholar 

  44. Behbod F, Rosen JM. Will cancer stem cells provide new therapeutic targets? Carcinogenesis 2004. Available at http://carcin.oupjournals.org/cgi/reprint/bgh293v1.

  45. Smith GH, Chepko G. Mammary epithelial stem cells. Microsc Res Tech 2001;52:190–203.

    Article  CAS  PubMed  Google Scholar 

  46. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105–11.

    Article  CAS  PubMed  Google Scholar 

  47. Sejrsen K, Purup S. Influence of prepubertal feeding level on milk yield potential of dairy heifers: A review. J Anim Sci 1997;75:828–35.

    CAS  PubMed  Google Scholar 

  48. Capuco AV, Smith JJ, Waldo DR, Rexroad CE, Jr. Influence of prepubertal dietary regimen on mammary growth of Holstein heifers. J Dairy Sci 1995;78:2709–25.

    CAS  PubMed  Google Scholar 

  49. Capuco AV, Erdman R, Dahl G, Meyer M, Van Amburgh M. Heifer nutrition prepubertal growth and development. Proceedings of the 50th Maryland Nutrition Conference for Feed Manufacturers and1st Mid-Atlantic Nutrition Conference. University of Maryland, 2003:102–15.

  50. Paape MJ, Tucker HA. Influence of length of dry period on subsequent lactation in the rat. J Dairy Sci 1969;52:518–22.

    CAS  PubMed  Google Scholar 

  51. Bauman DE, Everett RW, Weiland WH, Collier RJ. Production responses to bovine somatotropin in northeast dairy herds. J Dairy Sci 1999;82:2564–73.

    CAS  PubMed  Google Scholar 

  52. Annen EL, Collier RJ, McGuire MA, Vicini JL. Effects of dry period length on milk yield and mammary epithelial cells. J Dairy Sci 2004;87(Suppl E):E66–76.

    Google Scholar 

  53. Potten CS, Owen G, Booth D. Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci 2002;115:2381–88.

    CAS  PubMed  Google Scholar 

  54. Capuco AV, Ellis SE, Hale SA, Long E, Erdman RA, Zhao X, Paape MJ. Lactation persistency: Insights from mammary cell proliferation studies. J Anim Sci 2003;81(Suppl 3):18–31.

    CAS  PubMed  Google Scholar 

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Correspondence to A. V. Capuco.

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Capuco, A.V., Ellis, S. Bovine Mammary Progenitor Cells: Current Concepts and Future Directions. J Mammary Gland Biol Neoplasia 10, 5–15 (2005). https://doi.org/10.1007/s10911-005-2536-3

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