The Terminal End Bud: the Little Engine that Could

Journal of Mammary Gland Biology and Neoplasia

Volumn 22, Issue 2, 2017, Pages 93-108

  Paine, Ingrid S ^a   Lewis, Michael T ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Cap cell; Ductal elongation; Mammary gland; Terminal end bud

Indexed keywords

EPIDERMAL GROWTH FACTOR; ESTROGEN; FIBROBLAST GROWTH FACTOR; GROWTH HORMONE; HEPARANASE; MATRIX METALLOPROTEINASE; PROGESTERONE; TRANSFORMING GROWTH FACTOR BETA; WNT PROTEIN;

AXON GUIDANCE; BASEMENT MEMBRANE; BODY CELL; BREAST CANCER; BREAST CELL; BREAST DEVELOPMENT; BREAST TISSUE; CANCER MODEL; CAP CELL; CELL MIGRATION; COLLECTIVE MIGRATION; DEVELOPMENTAL BIOLOGY; EOSINOPHIL; EPITHELIAL MESENCHYMAL TRANSITION; ESTROGEN ACTIVITY; FIBROBLAST; HUMAN; MACROPHAGE; MAMMARY GLAND; MAMMARY GLAND FUNCTION; MAMMARY STEM CELL; MAMMARY STROMA; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; STROMA; TERMINAL END BUD; ANIMAL; BIOLOGICAL MODEL; BREAST; BREAST TUMOR; CYTOLOGY; FEMALE; PATHOLOGY; PHYSIOLOGY;

ANIMALS; BREAST; BREAST NEOPLASMS; FEMALE; HUMANS; MODELS, BIOLOGICAL;

EID: 85011661301     PISSN: 10833021     EISSN: 15737039     Source Type: Journal    
DOI: 10.1007/s10911-017-9372-0     Document Type: Review

References (146)

1. Veltmaat JM, et al. Identification of the mammary line in mouse by Wnt10b expression. Dev Dyn. 2004;229(2):349–56.
2. Sakakura T, et al. Biology of mammary fat pad in fetal mouse: capacity to support development of various fetal epithelia in vivo. Development. 1987;100(3):421–30.
3. Dunbar ME, et al. Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development. Development. 1999;126(16):3485–93.
4. Hogg NA, Harrison CJ, Tickle C. Lumen formation in the developing mouse mammary gland. J Embryol Exp Morphol. 1983;73:39–57.
5. Inman JL, et al. Mammary gland development: cell fate specification, stem cells and the microenvironment. Development. 2015;142(6):1028–42.
6. Hens JR, Wysolmerski JJ. Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Res. 2005;7(5):220–4.
7. Bresciani F. Effect of ovarian hormones on duration of DNA synthesis in cells of the C3h mouse mammary gland. Exp Cell Res. 1965;38:13–32.
8. Williams JM, Daniel CW. Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol. 1983;97(2):274–90.
9. Brisken C. Hormonal control of alveolar development and its implications for breast carcinogenesis. J Mammary Gland Biol Neoplasia. 2002;7(1):39–48.
10. McManaman JL, Neville MC. Mammary physiology and milk secretion. Adv Drug Deliv Rev. 2003;55(5):629–41.
11. Oakes SR, et al. Prolactin regulation of mammary gland development. J Mammary Gland Biol Neoplasia. 2008;13(1):13–28.
12. Monks J, et al. Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ. 2005;12(2):107–14.
13. Monks J, et al. Epithelial cells remove apoptotic epithelial cells during post-lactation involution of the mouse mammary gland. Biol Reprod. 2008;78(4):586–94.
14. Russo IH, Russo J. Developmental stage of the rat mammary gland as determinant of its susceptibility to 7,12-dimethylbenz[a]anthracene. J Natl Cancer Inst. 1978;61(6):1439–49.
15. Russo J, Russo IH. Influence of differentiation and cell kinetics on the susceptibility of the rat mammary gland to carcinogenesis. Cancer Res. 1980;40(8 Pt 1):2677–87.
16. Cline, J.M. and C.E. Wood, The Mammary Glands of Macaques. Toxicologic pathology, 2008. 36(7): p. 134 s–141 s.
17. Wood CE, Hester JM, Cline JM. Mammary gland development in early pubertal female macaques. Toxicol Pathol. 2007;35(6):795–805.
18. Capuco AV, Ellis SE. Comparative aspects of mammary gland development and homeostasis. Annual review of animal biosciences. 2013;1:179–202.
19. Howard BA, Gusterson BA. Human breast development. J Mammary Gland Biol Neoplasia. 2000;5(2):119–37.
20. Javed A, Lteif A. Development of the human breast. Semin Plast Surg. 2013;27(1):5–12.
21. Huebner RJ, Lechler T, Ewald AJ. Developmental stratification of the mammary epithelium occurs through symmetry-breaking vertical divisions of apically positioned luminal cells. Development. 2014;141(5):1085–94.
22. Hinck L, Silberstein GB. Key stages in mammary gland development: the mammary end bud as a motile organ. Breast Cancer Res. 2005;7(6):245–51.
23. Daniel CW, Smith GH. The mammary gland: a model for development. J Mammary Gland Biol Neoplasia. 1999;4(1):3–8.
24. Daniel CW, Strickland P, Friedmann Y. Expression and functional role of E- and P-cadherins in mouse mammary ductal morphogenesis and growth. Dev Biol. 1995;169(2):511–9.
25. Shamir ER, Ewald AJ. Adhesion in mammary development: novel roles for E-cadherin in individual and collective cell migration. Curr Top Dev Biol. 2015;112:353–82.
26. Shamir ER, et al. Twist1-induced dissemination preserves epithelial identity and requires E-cadherin. J Cell Biol. 2014;204(5):839–56.
27. Ewald AJ, et al. Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. Dev Cell. 2008;14(4):570–81.
28. Ewald AJ, et al. Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium. J Cell Sci. 2012;125(Pt 11):2638–54.
29. Silberstein GB, Daniel CW. Glycosaminoglycans in the basal lamina and extracellular matrix of the developing mouse mammary duct. Dev Biol. 1982;90(1):215–22.
30. Fata JE, Werb Z, Bissell MJ. Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes. Breast Cancer Res. 2004;6(1):1–11.
31. Keely PJ, Wu JE, Santoro SA. The spatial and temporal expression of the alpha 2 beta 1 integrin and its ligands, collagen I, collagen IV, and laminin, suggest important roles in mouse mammary morphogenesis. Differentiation. 1995;59(1):1–13.
32. Lochter A, Bissell MJ. Involvement of extracellular matrix constituents in breast cancer. Semin Cancer Biol. 1995;6(3):165–73.
33. Bai L, Rohrschneider LR. S-SHIP promoter expression marks activated stem cells in developing mouse mammary tissue. Genes Dev. 2010;24(17):1882–92.
34. Rios AC, et al. In situ identification of bipotent stem cells in the mammary gland. Nature. 2014;506(7488):322–7.
35. Hovey RC, Trott JF, Vonderhaar BK. Establishing a framework for the functional mammary gland: from endocrinology to morphology. J Mammary Gland Biol Neoplasia. 2002;7(1):17–38.
36. Neville MC, McFadden TB, Forsyth I. Hormonal regulation of mammary differentiation and milk secretion. J Mammary Gland Biol Neoplasia. 2002;7(1):49–66.
37. Grimm SL, et al. Keratin 6 is not essential for mammary gland development. Breast Cancer Res. 2006;8(3):R29.
38. Ismail PM, et al. A novel LacZ reporter mouse reveals complex regulation of the progesterone receptor promoter during mammary gland development. Mol Endocrinol. 2002;16(11):2475–89.
39. Humphreys RC, et al. Apoptosis in the terminal endbud of the murine mammary gland: a mechanism of ductal morphogenesis. Development. 1996;122(12):4013–22.
40. Paine I, et al. A geometrically-constrained mathematical model of mammary gland ductal elongation reveals novel cellular dynamics within the terminal end Bud. PLoS Comput Biol. 2016;12(4):e1004839.
41. Faulkin Jr LJ, Deome KB. Regulation of growth and spacing of gland elements in the mammary fat pad of the C3H mouse. J Natl Cancer Inst. 1960;24:953–69.
42. Deome KB, et al. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res. 1959;19(5):515–20.
43. Chepko G, Smith GH. Three division-competent, structurally-distinct cell populations contribute to murine mammary epithelial renewal. Tissue Cell. 1997;29(2):239–53.
44. Smith GH. Experimental mammary epithelial morphogenesis in an in vivo model: evidence for distinct cellular progenitors of the ductal and lobular phenotype. Breast Cancer Res Treat. 1996;39(1):21–31.
45. Kordon EC, Smith GH. An entire functional mammary gland may comprise the progeny from a single cell. Development. 1998;125(10):1921–30.
46. Srinivasan K, et al. Netrin-1/neogenin interaction stabilizes multipotent progenitor cap cells during mammary gland morphogenesis. Dev Cell. 2003;4(3):371–82.
47. Mailleux AA, et al. BIM regulates apoptosis during mammary ductal morphogenesis, and its absence reveals alternative cell death mechanisms. Dev Cell. 2007;12(2):221–34.
48. Lu P, et al. Genetic mosaic analysis reveals FGF receptor 2 function in terminal end buds during mammary gland branching morphogenesis. Dev Biol. 2008;321(1):77–87.
49. Van Keymeulen A, et al. Distinct stem cells contribute to mammary gland development and maintenance. Nature. 2011;479(7372):189–93.
50. Roarty K, et al. Ror2 regulates branching, differentiation, and actin-cytoskeletal dynamics within the mammary epithelium. J Cell Biol. 2015;208(3):351–66.
51. Huo Y, Macara IG. The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance. Nat Cell Biol. 2014;16(6):529–37.
52. Sakakura T, Nishizuka Y, Dawe CJ. Mesenchyme-dependent morphogenesis and epithelium-specific cytodifferentiation in mouse mammary gland. Science. 1976;194(4272):1439–41.
53. Zhang X, et al. FGF ligands of the postnatal mammary stroma regulate distinct aspects of epithelial morphogenesis. Development. 2014;141(17):3352–62.
54. Ingman WV, et al. Macrophages promote collagen fibrillogenesis around terminal end buds of the developing mammary gland. Dev Dyn. 2006;235(12):3222–9.
55. Gouon-Evans V, Rothenberg ME, Pollard JW. Postnatal mammary gland development requires macrophages and eosinophils. Development. 2000;127(11):2269–82.
56. Unsworth A, Anderson R, Britt K. Stromal fibroblasts and the immune microenvironment: partners in mammary gland biology and pathology? J Mammary Gland Biol Neoplasia. 2014;19(2):169–82.
57. Kleinberg DL, Feldman M, Ruan W. IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis. J Mammary Gland Biol Neoplasia. 2000;5(1):7–17.
58. Kamalati T, et al. HGF/SF in mammary epithelial growth and morphogenesis: in vitro and in vivo models. J Mammary Gland Biol Neoplasia. 1999;4(1):69–77.
59. Aupperlee MD, et al. Epidermal growth factor receptor (EGFR) signaling is a key mediator of hormone-induced leukocyte infiltration in the pubertal female mammary gland. Endocrinology. 2014;155(6):2301–13.
60. Horiuchi T, Weller PF. Expression of vascular endothelial growth factor by human eosinophils: upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5. Am J Respir Cell Mol Biol. 1997;17(1):70–7.
61. Brisken C, O'Malley B. Hormone action in the mammary gland. Cold Spring Harb Perspect Biol. 2010;2(12):a003178.
62. Yart L, et al. Role of ovarian secretions in mammary gland development and function in ruminants. Animal. 2014;8(1):72–85.
63. Pedram A, et al. Membrane-localized estrogen receptor alpha is required for normal organ development and function. Dev Cell. 2014;29(4):482–90.
64. Pedram A, et al. Developmental phenotype of a membrane only estrogen receptor alpha (MOER) mouse. J Biol Chem. 2009;284(6):3488–95.
65. Daniel CW, Silberstein GB, Strickland P. Direct action of 17 beta-estradiol on mouse mammary ducts analyzed by sustained release implants and steroid autoradiography. Cancer Res. 1987;47(22):6052–7.
66. Bocchinfuso WP, Korach KS. Mammary gland development and tumorigenesis in estrogen receptor knockout mice. J Mammary Gland Biol Neoplasia. 1997;2(4):323–34.
67. Sternlicht MD, Sunnarborg SW. The ADAM17-amphiregulin-EGFR axis in mammary development and cancer. J Mammary Gland Biol Neoplasia. 2008;13(2):181–94.
68. Ciarloni L, Mallepell S, Brisken C. Amphiregulin is an essential mediator of estrogen receptor alpha function in mammary gland development. Proc Natl Acad Sci U S A. 2007;104(13):5455–60.
69. Kenney NJ, et al. Effect of exogenous epidermal-like growth factors on mammary gland development and differentiation in the estrogen receptor-alpha knockout (ERKO) mouse. Breast Cancer Res Treat. 2003;79(2):161–73.
70. Mallepell S, et al. Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci U S A. 2006;103(7):2196–201.
71. Niswender GD, et al. Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev. 2000;80(1):1–29.
72. Lee HJ, et al. Progesterone drives mammary secretory differentiation via RankL-mediated induction of Elf5 in luminal progenitor cells. Development. 2013;140(7):1397–401.
73. Lydon JP, et al. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 1995;9(18):2266–78.
74. Haslam SZ. Progesterone effects on deoxyribonucleic acid synthesis in normal mouse mammary glands. Endocrinology. 1988;122(2):464–70.
75. 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(5):1835–44.
76. Ruan W, Monaco ME, Kleinberg DL. Progesterone stimulates mammary gland ductal morphogenesis by synergizing with and enhancing insulin-like growth factor-I action. Endocrinology. 2005;146(3):1170–8.
77. Humphreys RC, et al. Mammary gland development is mediated by both stromal and epithelial progesterone receptors. Mol Endocrinol. 1997;11(6):801–11.
78. Humphreys RC, et al. Use of PRKO mice to study the role of progesterone in mammary gland development. J Mammary Gland Biol Neoplasia. 1997;2(4):343–54.
79. Aupperlee MD, et al. Amphiregulin mediates progesterone-induced mammary ductal development during puberty. Breast Cancer Res. 2013;15(3):R44.
80. Hull KL, Harvey S. Growth hormone and reproduction: a review of endocrine and autocrine/paracrine interactions. Int J Endocrinol. 2014;2014:234014.
81. Silberstein GB, et al. Essential role of endogenous estrogen in directly stimulating mammary growth demonstrated by implants containing pure antiestrogens. Endocrinology. 1994;134(1):84–90.
82. Zeps N, et al. Estrogen receptor-negative epithelial cells in mouse mammary gland development and growth. Differentiation. 1998;62(5):221–6.
83. Macias H, Hinck L. Mammary gland development. Wiley Interdiscip Rev Dev Biol. 2012;1(4):533–57.
84. Loladze AV, et al. Epithelial-specific and stage-specific functions of insulin-like growth factor-I during postnatal mammary development. Endocrinology. 2006;147(11):5412–23.
85. Wang Z. Transactivation of Epidermal Growth Factor Receptor by G Protein-Coupled Receptors: Recent Progress, Challenges and Future Research. Int J Mol Sci. 2016;17(1)
86. Sanderson MP, Dempsey PJ, Dunbar AJ. Control of ErbB signaling through metalloprotease mediated ectodomain shedding of EGF-like factors. Growth Factors. 2006;24(2):121–36.
87. Bergers G, Coussens LM. Extrinsic regulators of epithelial tumor progression: metalloproteinases. Curr Opin Genet Dev. 2000;10(1):120–7.
88. Schroeder JA, Lee DC. Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. Cell Growth Differ. 1998;9(6):451–64.
89. Coleman S, Silberstein GB, Daniel CW. Ductal morphogenesis in the mouse mammary gland: evidence supporting a role for epidermal growth factor. Dev Biol. 1988;127(2):304–15.
90. Sebastian J, et al. Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. Cell Growth Differ. 1998;9(9):777–85.
91. Xie W, et al. Targeted expression of a dominant negative epidermal growth factor receptor in the mammary gland of transgenic mice inhibits pubertal mammary duct development. Mol Endocrinol. 1997;11(12):1766–81.
92. Tidcombe H, et al. Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality. Proc Natl Acad Sci U S A. 2003;100(14):8281–6.
93. Jackson-Fisher AJ, et al. ErbB2 is required for ductal morphogenesis of the mammary gland. Proc Natl Acad Sci U S A. 2004;101(49):17138–43.
94. Hynes NE, Watson CJ. Mammary gland growth factors: roles in normal development and in cancer. Cold Spring Harb Perspect Biol. 2010;2(8):a003186.
95. Pond AC, et al. Fibroblast growth factor receptor signaling is essential for normal mammary gland development and stem cell function. Stem Cells. 2013;31(1):178–89.
96. Astigiano S, Damonte P, Barbieri O. Inhibition of ductal morphogenesis in the mammary gland of WAP -fgf4 transgenic mice. Anat Embryol. 2003;206(6):471–8.
97. Fata JE, et al. The MAPK(ERK-1,2) pathway integrates distinct and antagonistic signals from TGFalpha and FGF7 in morphogenesis of mouse mammary epithelium. Dev Biol. 2007;306(1):193–207.
98. Cui Y, Li Q. Expression and functions of fibroblast growth factor 10 in the mouse mammary gland. Int J Mol Sci. 2013;14(2):4094–105.
99. Itoh, N., FGF10: a multifunctional mesenchymal-epithelial signaling growth factor in development, health, and disease. Cytokine Growth Factor Rev, 2015.
100. Parsa S, et al. Terminal end bud maintenance in mammary gland is dependent upon FGFR2b signaling. Dev Biol. 2008;317(1):121–31.
101. Vaidya A, Kale VP. TGF-beta signaling and its role in the regulation of hematopoietic stem cells. Syst Synth Biol. 2015;9(1–2):1–10.
102. Moses H, Barcellos-Hoff MH. TGF-beta biology in mammary development and breast cancer. Cold Spring Harb Perspect Biol. 2011;3(1):a003277.
103. Silberstein GB, Daniel CW. Reversible inhibition of mammary gland growth by transforming growth factor-beta. Science. 1987;237(4812):291–3.
104. Robinson SD, et al. Regulated expression and growth inhibitory effects of transforming growth factor-beta isoforms in mouse mammary gland development. Development. 1991;113(3):867–78.
105. Soriano JV, et al. Roles of hepatocyte growth factor/scatter factor and transforming growth factor-beta1 in mammary gland ductal morphogenesis. J Mammary Gland Biol Neoplasia. 1998;3(2):133–50.
106. Silberstein GB, et al. Epithelium-dependent extracellular matrix synthesis in transforming growth factor-beta 1-growth-inhibited mouse mammary gland. J Cell Biol. 1990;110(6):2209–19.
107. Pierce Jr DF, et al. Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1. Genes Dev. 1993;7(12A):2308–17.
108. Bottinger EP, et al. Transgenic mice overexpressing a dominant-negative mutant type II transforming growth factor beta receptor show enhanced tumorigenesis in the mammary gland and lung in response to the carcinogen 7,12-dimethylbenz-[a]-anthracene. Cancer Res. 1997;57(24):5564–70.
109. Barcellos-Hoff, M.H. and F.A. Cucinotta, New tricks for an old fox: impact of TGFbeta on the DNA damage response and genomic stability. Sci Signal, 2014. 7(341): p. re5.
110. Staal, F.J., A. Chhatta, and H. Mikkers, Caught in a Wnt storm: complexities of Wnt signalling in hematopoiesis. Exp Hematol, 2016.
111. Yu, Q.C., E.M. Verheyen, and Y.A. Zeng,. Mammary Development and Breast Cancer: A Wnt Perspective. Cancers (Basel), 2016. 8(7).
112. Komiya Y, Habas R. Wnt signal transduction pathways. Organogenesis. 2008;4(2):68–75.
113. Lane TF, Leder P. Wnt-10b directs hypermorphic development and transformation in mammary glands of male and female mice. Oncogene. 1997;15(18):2133–44.
114. Buhler TA, et al. Localization and quantification of Wnt-2 gene expression in mouse mammary development. Dev Biol. 1993;155(1):87–96.
115. Lindvall C, et al. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development. PLoS One. 2009;4(6):e5813.
116. Badders NM, et al. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage. PLoS One. 2009;4(8):e6594.
117. Lindvall C, et al. The Wnt signaling receptor Lrp5 is required for mammary ductal stem cell activity and Wnt1-induced tumorigenesis. J Biol Chem. 2006;281(46):35081–7.
118. Rajaram RD, et al. Progesterone and Wnt4 control mammary stem cells via myoepithelial crosstalk. EMBO J. 2015;34(5):641–52.
119. Roarty K, Serra R. Wnt5a is required for proper mammary gland development and TGF-beta-mediated inhibition of ductal growth. Development. 2007;134(21):3929–39.
120. Strickland P, et al. Slit2 and netrin 1 act synergistically as adhesive cues to generate tubular bi-layers during ductal morphogenesis. Development. 2006;133(5):823–32.
121. Ballard MS, et al. Mammary stem cell self-renewal is regulated by Slit2/Robo1 signaling through SNAI1 and mINSC. Cell Rep. 2015;13(2):290–301.
122. Morris JS, et al. Involvement of axonal guidance proteins and their signaling partners in the developing mouse mammary gland. J Cell Physiol. 2006;206(1):16–24.
123. Haeger A, et al. Collective cell migration: guidance principles and hierarchies. Trends Cell Biol. 2015;25(9):556–66.
124. Goldenberg VE, Goldenberg NS, Sommers SC. Comparative ultrastructure of atypical ductal hyperplasia, intraductal carcinoma, and infiltrating ductal carcinoma of the breast. Cancer. 1969;24(6):1152–69.
125. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8.
126. Yin Y, et al. CD151 represses mammary gland development by maintaining the niches of progenitor cells. Cell Cycle. 2014;13(17):2707–22.
127. Basham KJ, et al. Chemical genetic screen reveals a role for desmosomal adhesion in mammary branching morphogenesis. J Biol Chem. 2013;288(4):2261–70.
128. Nassour M, et al. Slug controls stem/progenitor cell growth dynamics during mammary gland morphogenesis. PLoS One. 2012;7(12):e53498.
129. Gomes AM, et al. Mammary branching morphogenesis requires reciprocal signaling by heparanase and MMP-14. J Cell Biochem. 2015;116(8):1668–79.
130. Mori H, et al. Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin beta1. Development. 2013;140(2):343–52.
131. Wiseman BS, et al. Site-specific inductive and inhibitory activities of MMP-2 and MMP-3 orchestrate mammary gland branching morphogenesis. J Cell Biol. 2003;162(6):1123–33.
132. Gudjonsson T, et al. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci. 2002;115(Pt 1):39–50.
133. Maller O, Martinson H, Schedin P. Extracellular matrix composition reveals complex and dynamic stromal-epithelial interactions in the mammary gland. J Mammary Gland Biol Neoplasia. 2010;15(3):301–18.
134. Nelson CM, et al. Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science. 2006;314(5797):298–300.
135. Schedin P, Keely PJ. Mammary gland ECM remodeling, stiffness, and mechanosignaling in normal development and tumor progression. Cold Spring Harb Perspect Biol. 2011;3(1):a003228.
136. Wang H, et al. Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly. Proc Natl Acad Sci U S A. 2013;110(1):163–8.
137. Visvader JE, Stingl J. Mammary stem cells and the differentiation hierarchy: current status and perspectives. Genes Dev. 2014;28(11):1143–58.
138. Prat A, Perou CM. Mammary development meets cancer genomics. Nat Med. 2009;15(8):842–4.
139. Polyak K. Heterogeneity in breast cancer. J Clin Invest. 2011;121(10):3786–8.
140. Stingl J, Caldas C. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nat Rev Cancer. 2007;7(10):791–9.
141. Rossiter H, et al. Inactivation of VEGF in mammary gland epithelium severely compromises mammary gland development and function. FASEB J. 2007;21(14):3994–4004.
142. Folkman J. Fighting cancer by attacking its blood supply. Sci Am. 1996;275(3):150–4.
143. Leung DW, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246(4935):1306–9.
144. Wiseman BS, Werb Z. Stromal effects on mammary gland development and breast cancer. Science. 2002;296(5570):1046–9.
145. Chang CH, et al. Mammary stem cells and tumor-initiating cells are more resistant to apoptosis and exhibit increased DNA repair activity in response to DNA damage. Stem Cell Reports. 2015;5(3):378–91.
146. Gjorevski N, Nelson CM. Integrated morphodynamic signalling of the mammary gland. Nat Rev Mol Cell Biol. 2011;12(9):581–93.