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Deciphering the molecular basis of breast cancer metastasis with mouse models

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Abstract

Breast cancer begins as a localized disease, but has the potential to spread to distant sites within the body. This process—known as metastasis—is the leading cause of death from breast cancer. Whether the ability of cancer cells to metastasize is an intrinsic or acquired feature is currently a topic of considerable debate. Nevertheless, the key cellular events required for metastasis are generally accepted. These include invasion of the surrounding stromal tissue, intravasation, evasion of programmed cell death, arrest within the vasculature at a distant site, extravasation, and establishment and growth within a new microenvironment. The development of mouse models that faithfully mimic critical aspects of human neoplasia has been instrumental in framing our current understanding of multistage carcinogenesis. This review examines the advantages and limitations of existing murine models for mammary carcinogenesis for probing the molecular mechanisms that contribute to metastasis, as well as non-invasive tumor imaging approaches to facilitate these investigations.

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References

  1. Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 2005;7:211–7.

    Article  PubMed  CAS  Google Scholar 

  2. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860–7.

    Article  PubMed  CAS  Google Scholar 

  3. Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006;124:263–6.

    Article  PubMed  CAS  Google Scholar 

  4. Tan TT, Coussens LM. Humoral immunity, inflammation and cancer. Curr Opin Immunol 2007;19:209–16.

    Article  PubMed  CAS  Google Scholar 

  5. Duda DG, Fukumura D, Munn LL, Booth MF, Brown EB, Huang P, et al. Differential transplantability of tumor-associated stromal cells. Cancer Res 2004;64:5920–4.

    Article  PubMed  CAS  Google Scholar 

  6. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 1999;59:5002–11.

    PubMed  CAS  Google Scholar 

  7. Kim JB, Stein R, O’Hare MJ. Tumour–stromal interactions in breast cancer: the role of stroma in tumourigenesis. Tumour Biol 2005;26:173–85.

    Article  PubMed  Google Scholar 

  8. Matrisian LM, Cunha GR, Mohla S. Epithelial–stromal interactions and tumor progression: meeting summary and future directions. Cancer Res 2001;61:3844–6.

    PubMed  CAS  Google Scholar 

  9. Kim JB, O’Hare MJ, Stein R. Models of breast cancer: is merging human and animal models the future? Breast Cancer Res 2004;6:22–30.

    Article  PubMed  CAS  Google Scholar 

  10. Parker B, Sukumar S. Distant metastasis in breast cancer: molecular mechanisms and therapeutic targets. Cancer Biol Ther 2003;2:14–21.

    PubMed  Google Scholar 

  11. Raubenheimer EJ, Noffke CE. Pathogenesis of bone metastasis: a review. J Oral Pathol & Med 2006;35:129–35.

    Article  CAS  Google Scholar 

  12. Yoneda T. Arterial microvascularization and breast cancer colonization in bone. Histol Histopathol 1997;12:1145–9.

    PubMed  CAS  Google Scholar 

  13. Rosol TJ, Tannehill-Gregg SH, Corn S, Schneider A, McCauley LK. Animal models of bone metastasis. Cancer Treat Res 2004;118:47–81.

    PubMed  Google Scholar 

  14. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889;i:571–3.

    Article  Google Scholar 

  15. Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD, Muller WJ. Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc Natl Acad Sci U S A 1992;89:10578–82.

    Article  PubMed  CAS  Google Scholar 

  16. Moody SE, Sarkisian CJ, Hahn KT, Gunther EJ, Pickup S, Dugan KD, et al. Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2002;2:451–61.

    Article  PubMed  CAS  Google Scholar 

  17. McCormack SJ, Weaver Z, Deming S, Natarajan G, Torri J, Johnson MD, et al. Myc/p53 interactions in transgenic mouse mammary development, tumorigenesis and chromosomal instability. Oncogene 1998;16:2755–66.

    Article  PubMed  CAS  Google Scholar 

  18. D’Cruz CM, Gunther EJ, Boxer RB, Hartman JL, Sintasath L, Moody SE, et al. c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 2001;7:235–9.

    Article  PubMed  CAS  Google Scholar 

  19. Guy CT, Cardiff RD, Muller WJ. Induction of mammary tumors by expression of polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol 1992;12:954–61.

    PubMed  CAS  Google Scholar 

  20. Chatterjee G, Rosner A, Han Y, Zelazny ET, Li B, Cardiff RD, et al. Acceleration of mouse mammary tumor virus-induced murine mammary tumorigenesis by a p53 172H transgene: influence of FVB background on tumor latency and identification of novel sites of proviral insertion. Am J Pathol 2002;161:2241–53.

    PubMed  CAS  Google Scholar 

  21. Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature 1994;369:669–71.

    Article  PubMed  CAS  Google Scholar 

  22. Tsukamoto AS, Grosschedl R, Guzman RC, Parslow T, Varmus HE. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 1988;55:619–25.

    Article  PubMed  CAS  Google Scholar 

  23. Imbert A, Eelkema R, Jordan S, Feiner H, Cowin P. Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland. J Cell Biol 2001;153:555–68.

    Article  PubMed  CAS  Google Scholar 

  24. Jhappan C, Stahle C, Harkins RN, Fausto N, Smith GH, Merlino GT. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 1990;61:1137–46.

    Article  PubMed  CAS  Google Scholar 

  25. Matsui Y, Halter SA, Holt JT, Hogan BL, Coffey RJ. Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice. Cell 1990;61:1147–55.

    Article  PubMed  CAS  Google Scholar 

  26. Sandgren EP, Luetteke NC, Palmiter RD, Brinster RL, Lee DC. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 1990;61:1121–35.

    Article  PubMed  CAS  Google Scholar 

  27. Nielsen LL, Discafani CM, Gurnani M, Tyler RD. Histopathology of salivary and mammary gland tumors in transgenic mice expressing a human Ha-ras oncogene. Cancer Res 1991;51:3762–7.

    PubMed  CAS  Google Scholar 

  28. Gallahan D, Jhappan C, Robinson G, Hennighausen L, Sharp R, Kordon E, et al. Expression of a truncated Int3 gene in developing secretory mammary epithelium specifically retards lobular differentiation resulting in tumorigenesis. Cancer Res 1996;56:1775–85.

    PubMed  CAS  Google Scholar 

  29. Pravtcheva DD, Wise TL. Metastasizing mammary carcinomas in H19 enhancers-Igf2 transgenic mice. J Exp Zool 1998;281:43–57.

    Article  PubMed  CAS  Google Scholar 

  30. Teuliere J, Faraldo MM, Deugnier MA, Shtutman M, Ben-Ze’ev A, Thiery JP, et al. Targeted activation of beta-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia. Development 2005;132:267–77.

    Article  PubMed  CAS  Google Scholar 

  31. Gallego MI, Bierie B, Hennighausen L. Targeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways. Oncogene 2003;22:8498–508.

    Article  PubMed  CAS  Google Scholar 

  32. Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 1987;49:465–75.

    Article  PubMed  CAS  Google Scholar 

  33. Siegel PM, Shu W, Cardiff RD, Muller WJ, Massague J. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci U S A 2003;100:8430–5.

    Article  PubMed  CAS  Google Scholar 

  34. Hosokawa Y, Papanikolaou A, Cardiff RD, Yoshimoto K, Bernstein M, Wang TC, et al. In vivo analysis of mammary and non-mammary tumorigenesis in MMTV-cyclin D1 transgenic mice deficient in p53. Transgenic Res 2001;10:471–8.

    Article  PubMed  CAS  Google Scholar 

  35. Kwan H, Pecenka V, Tsukamoto A, Parslow TG, Guzman R, Lin TP, et al. Transgenes expressing the Wnt-1 and int-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice. Mol Cell Biol 1992;12:147–54.

    PubMed  CAS  Google Scholar 

  36. Jackson-Fisher AJ, Bellinger G, Shum E, Duong JK, Perkins AS, Gassmann M, et al. Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4. Oncogene 2006;25:5664–72.

    Article  PubMed  CAS  Google Scholar 

  37. Lin EY, Jones JG, Li P, Zhu L, Whitney KD, Muller WJ, et al. Progression to malignancy in the polyoma middle T oncoprotein mouse breast cancer model provides a reliable model for human diseases. Am J Pathol 2003;163:2113–26.

    PubMed  Google Scholar 

  38. Granovsky M, Fata J, Pawling J, Muller WJ, Khokha R, Dennis JW. Suppression of tumor growth and metastasis in Mgat5-deficient mice. Nat Med 2000;6:306–12.

    Article  PubMed  CAS  Google Scholar 

  39. Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 2001;193:727–40.

    Article  PubMed  CAS  Google Scholar 

  40. Bugge TH, Lund LR, Kombrinck KK, Nielsen BS, Holmback K, Drew AF, et al. Reduced metastasis of Polyoma virus middle T antigen-induced mammary cancer in plasminogen-deficient mice. Oncogene 1998;16:3097–104.

    Article  PubMed  CAS  Google Scholar 

  41. Gutierrez LS, Schulman A, Brito-Robinson T, Noria F, Ploplis VA, Castellino FJ. Tumor development is retarded in mice lacking the gene for urokinase-type plasminogen activator or its inhibitor, plasminogen activator inhibitor-1. Cancer Res 2000;60:5839–47.

    PubMed  CAS  Google Scholar 

  42. Hakem A, Sanchez-Sweatman O, You-Ten A, Duncan G, Wakeham A, Khokha R, et al. RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis. Genes Dev 2005;19:1974–9.

    Article  PubMed  CAS  Google Scholar 

  43. Nagle JA, Ma Z, Byrne MA, White MF, Shaw LM. Involvement of insulin receptor substrate 2 in mammary tumor metastasis. Mol Cell Biol 2004;24:9726–35.

    Article  PubMed  CAS  Google Scholar 

  44. Cuevas BD, Winter-Vann AM, Johnson NL, Johnson GL. MEKK1 controls matrix degradation and tumor cell dissemination during metastasis of polyoma middle-T driven mammary cancer. Oncogene 2006;25:4998–5010.

    Article  PubMed  CAS  Google Scholar 

  45. Peace BE, Toney-Earley K, Collins MH, Waltz SE. Ron receptor signaling augments mammary tumor formation and metastasis in a murine model of breast cancer. Cancer Res 2005;65:1285–93.

    Article  PubMed  CAS  Google Scholar 

  46. Spicer AP, Rowse GJ, Lidner TK, Gendler SJ. Delayed mammary tumor progression in Muc-1 null mice. J Biol Chem 1995;270:30093–101.

    Article  PubMed  CAS  Google Scholar 

  47. Cowin P, Rowlands TM, Hatsell SJ. Cadherins and catenins in breast cancer. Curr Opin Cell Biol 2005;17:499–508.

    Article  PubMed  CAS  Google Scholar 

  48. Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 1998;153:333–9.

    PubMed  CAS  Google Scholar 

  49. Birchmeier W, Behrens J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1994;1198:11–26.

    PubMed  CAS  Google Scholar 

  50. Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 2002;21:3241–6.

    Article  PubMed  CAS  Google Scholar 

  51. Strathdee G. Epigenetic versus genetic alterations in the inactivation of E-cadherin. Semin Cancer Biol 2002;12:373–9.

    Article  PubMed  CAS  Google Scholar 

  52. Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, et al. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat Cell Biol 2002;4:222–31.

    Article  CAS  Google Scholar 

  53. Vleminckx K, Vakaet L, Jr., Mareel M, Fiers W, van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 1991;66:107–19.

    Article  PubMed  CAS  Google Scholar 

  54. Mbalaviele G, Dunstan CR, Sasaki A, Williams PJ, Mundy GR, Yoneda T. E-cadherin expression in human breast cancer cells suppresses the development of osteolytic bone metastases in an experimental metastasis model. Cancer Res 1996;56:4063–70.

    PubMed  CAS  Google Scholar 

  55. Wilding J, Vousden KH, Soutter WP, McCrea PD, Del Buono R, Pignatelli M. E-cadherin transfection down-regulates the epidermal growth factor receptor and reverses the invasive phenotype of human papilloma virus-transfected keratinocytes. Cancer Res 1996;56:5285–92.

    PubMed  CAS  Google Scholar 

  56. Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 1998;392:190–3.

    Article  PubMed  CAS  Google Scholar 

  57. Derksen PW, Liu X, Saridin F, van der Gulden H, Zevenhoven J, Evers B, et al. Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell 2006;10:437–49.

    Article  PubMed  CAS  Google Scholar 

  58. Hazan RB, Phillips GR, Qiao RF, Norton L, Aaronson SA. Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol 2000;148:779–90.

    Article  PubMed  CAS  Google Scholar 

  59. Li G, Satyamoorthy K, Herlyn M. N-cadherin-mediated intercellular interactions promote survival and migration of melanoma cells. Cancer Res 2001;61:3819–25.

    PubMed  CAS  Google Scholar 

  60. Nieman MT, Prudoff RS, Johnson KR, Wheelock MJ. N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol 1999;147:631–44.

    Article  PubMed  CAS  Google Scholar 

  61. Hazan RB, Qiao R, Keren R, Badano I, Suyama K. Cadherin switch in tumor progression. Ann N Y Acad Sci 2004;1014:155–63.

    Article  PubMed  CAS  Google Scholar 

  62. Cavallaro U, Christofori G. Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough. Biochim Biophys Acta 2001;1552:39–45.

    PubMed  CAS  Google Scholar 

  63. Wong AS, Gumbiner BM. Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin. J Cell Biol 2003;161:1191–203.

    Article  PubMed  CAS  Google Scholar 

  64. Luo J, Lubaroff DM, Hendrix MJ. Suppression of prostate cancer invasive potential and matrix metalloproteinase activity by E-cadherin transfection. Cancer Res 1999;59:3552–6.

    PubMed  CAS  Google Scholar 

  65. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Jr., Davidson NE, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673–84.

    Article  PubMed  CAS  Google Scholar 

  66. Steeghs N, Nortier JW, Gelderblom H. Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Ann Surg Oncol 2006.

  67. Ruoslahti E, Noble NA, Kagami S, Border WA. Integrins. Kidney Inter Suppl 1994;44:S17–22.

    CAS  Google Scholar 

  68. Schwartz MA, Schaller MD, Ginsberg MH. Integrins: emerging paradigms of signal transduction. Annu Rev Cell Dev Biol 1995;11:549–99.

    Article  PubMed  CAS  Google Scholar 

  69. Taverna D, Moher H, Crowley D, Borsig L, Varki A, Hynes RO. Increased primary tumor growth in mice null for beta3- or beta3/beta5-integrins or selectins. Proc Natl Acad Sci U S A 2004;101:763–8.

    Article  PubMed  CAS  Google Scholar 

  70. Felding-Habermann B. Tumor cell-platelet interaction in metastatic disease. Haemostasis 2001;31(Suppl 1):55–8.

    PubMed  CAS  Google Scholar 

  71. Bakewell SJ, Nestor P, Prasad S, Tomasson MH, Dowland N, Mehrotra M, et al. Platelet and osteoclast beta3 integrins are critical for bone metastasis. Proc Natl Acad Sci U S A 2003;100:14205–10.

    Article  PubMed  CAS  Google Scholar 

  72. Reynolds LE, Wyder L, Lively JC, Taverna D, Robinson SD, Huang X, et al. Enhanced pathological angiogenesis in mice lacking beta3 integrin or beta3 and beta5 integrins. Nat Med 2002;8:27–34.

    Article  PubMed  CAS  Google Scholar 

  73. Johnson JP. Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev 1999;18:345–57.

    Article  PubMed  CAS  Google Scholar 

  74. Roesler J, Srivatsan E, Moatamed F, Peters J, Livingston EH. Tumor suppressor activity of neural cell adhesion molecule in colon carcinoma. Am J Surg 1997;174:251–7.

    Article  PubMed  CAS  Google Scholar 

  75. Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer 2004;4:118–32.

    PubMed  CAS  Google Scholar 

  76. Perl AK, Dahl U, Wilgenbus P, Cremer H, Semb H, Christofori G. Reduced expression of neural cell adhesion molecule induces metastatic dissemination of pancreatic beta tumor cells. Nat Med 1999;5:286–91.

    Article  PubMed  CAS  Google Scholar 

  77. Crnic I, Strittmatter K, Cavallaro U, Kopfstein L, Jussila L, Alitalo K, et al. Loss of neural cell adhesion molecule induces tumor metastasis by up-regulating lymphangiogenesis. Cancer Res 2004;64:8630–8.

    Article  PubMed  CAS  Google Scholar 

  78. Shih LM, Hsu MY, Palazzo JP, Herlyn M. The cell-cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast carcinoma. Am J Pathol 1997;151:745–51.

    PubMed  CAS  Google Scholar 

  79. Luo W, Wood CG, Earley K, Hung MC, Lin SH. Suppression of tumorigenicity of breast cancer cells by an epithelial cell adhesion molecule (C-CAM1): the adhesion and growth suppression are mediated by different domains. Oncogene 1997;14:1697–704.

    Article  PubMed  CAS  Google Scholar 

  80. Plunkett TA, Ellis PA. CEACAM1: a marker with a difference or more of the same? J Clin Oncol 2002;20:4273–5.

    PubMed  Google Scholar 

  81. Obrink B. CEA adhesion molecules: multifunctional proteins with signal-regulatory properties. Curr Opin Cell Biol 1997;9:616–26.

    Article  PubMed  CAS  Google Scholar 

  82. Wagener C, Ergun S. Angiogenic properties of the carcinoembryonic antigen-related cell adhesion molecule 1. Exp Cell Res 2000;261:19–24.

    Article  PubMed  CAS  Google Scholar 

  83. Koch AE, Halloran MM, Haskell CJ, Shah MR, Polverini PJ. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 1995;376:517–9.

    Article  PubMed  CAS  Google Scholar 

  84. Kirshner J, Chen CJ, Liu P, Huang J, Shively JE. CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture. Proc Natl Acad Sci U S A 2003;100:521–6.

    Article  PubMed  CAS  Google Scholar 

  85. Meier F, Busch S, Gast D, Goppert A, Altevogt P, Maczey E, et al. The adhesion molecule L1 (CD171) promotes melanoma progression. Int J Cancer 2006;119:549–55.

    Article  PubMed  CAS  Google Scholar 

  86. Fogel M, Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Smirnov A, et al. L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet 2003;362:869–75.

    Article  PubMed  CAS  Google Scholar 

  87. Kopfstein L, Christofori G. Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment. Cell Mol Life Sci 2006;63:449–68.

    Article  PubMed  CAS  Google Scholar 

  88. Calvo A, Xiao N, Kang J, Best CJ, Leiva I, Emmert-Buck MR, et al. Alterations in gene expression profiles during prostate cancer progression: functional correlations to tumorigenicity and down-regulation of selenoprotein-P in mouse and human tumors. Cancer Res 2002;62:5325–35.

    PubMed  CAS  Google Scholar 

  89. Thies A, Schachner M, Moll I, Berger J, Schulze HJ, Brunner G, et al. Overexpression of the cell adhesion molecule L1 is associated with metastasis in cutaneous malignant melanoma. Eur J Cancer 2002;38:1708–16.

    Article  PubMed  CAS  Google Scholar 

  90. Shtutman M, Levina E, Ohouo P, Baig M, Roninson IB. Cell adhesion molecule L1 disrupts E-cadherin-containing adherens junctions and increases scattering and motility of MCF7 breast carcinoma cells. Cancer Res 2006;66:11370–80.

    Article  PubMed  CAS  Google Scholar 

  91. Mechtersheimer S, Gutwein P, Agmon-Levin N, Stoeck A, Oleszewski M, Riedle S, et al. Ectodomain shedding of L1 adhesion molecule promotes cell migration by autocrine binding to integrins. J Cell Biol 2001;155:661–73.

    Article  PubMed  CAS  Google Scholar 

  92. Thelen K, Kedar V, Panicker AK, Schmid RS, Midkiff BR, Maness PF. The neural cell adhesion molecule L1 potentiates integrin-dependent cell migration to extracellular matrix proteins. J Neurosci 2002;22:4918–31.

    PubMed  CAS  Google Scholar 

  93. Voura EB, Ramjeesingh RA, Montgomery AM, Siu CH. Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells. Mol Biol Cell 2001;12:2699–710.

    PubMed  CAS  Google Scholar 

  94. Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze’ev A. Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev 2002;16:2058–72.

    Article  PubMed  CAS  Google Scholar 

  95. Gavert N, Conacci-Sorrell M, Gast D, Schneider A, Altevogt P, Brabletz T, et al. L1, a novel target of beta-catenin signaling, transforms cells and is expressed at the invasive front of colon cancers. J Cell Biol 2005;168:633–42.

    Article  PubMed  CAS  Google Scholar 

  96. Silletti S, Yebra M, Perez B, Cirulli V, McMahon M, Montgomery AM. Extracellular signal-regulated kinase (ERK)-dependent gene expression contributes to L1 cell adhesion molecule-dependent motility and invasion. J Biol Chem 2004;279:28880–8.

    Article  PubMed  CAS  Google Scholar 

  97. Primiano T, Baig M, Maliyekkel A, Chang BD, Fellars S, Sadhu J, et al. Identification of potential anticancer drug targets through the selection of growth-inhibitory genetic suppressor elements. Cancer Cell 2003;4:41–53.

    Article  PubMed  CAS  Google Scholar 

  98. Arlt MJ, Novak-Hofer I, Gast D, Gschwend V, Moldenhauer G, Grunberg J, et al. Efficient inhibition of intra-peritoneal tumor growth and dissemination of human ovarian carcinoma cells in nude mice by anti-L1-cell adhesion molecule monoclonal antibody treatment. Cancer Res 2006;66:936–43.

    Article  PubMed  CAS  Google Scholar 

  99. Huszar M, Moldenhauer G, Gschwend V, Ben-Arie A, Altevogt P, Fogel M. Expression profile analysis in multiple human tumors identifies L1 (CD171) as a molecular marker for differential diagnosis and targeted therapy. Hum Pathol 2006;37:1000–8.

    Article  PubMed  CAS  Google Scholar 

  100. Barcellos-Hoff MH, Aggeler J, Ram TG, Bissell MJ. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development 1989;105:223–35.

    PubMed  CAS  Google Scholar 

  101. Lemaitre V, D’Armiento J. Matrix metalloproteinases in development and disease. Birth Defects Res C Embryo Today 2006;78:1–10.

    Article  PubMed  CAS  Google Scholar 

  102. Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T. Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 2003;253:269–85.

    Article  PubMed  CAS  Google Scholar 

  103. Chang C, Werb Z. The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol 2001;11:S37–43.

    PubMed  CAS  Google Scholar 

  104. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 2000;1477:267–83.

    PubMed  CAS  Google Scholar 

  105. Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 2006;25:9–34.

    Article  PubMed  CAS  Google Scholar 

  106. Sternlicht MD, Lochter A, Sympson CJ, Huey B, Rougier JP, Gray JW, et al. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 1999;98:137–46.

    Article  PubMed  CAS  Google Scholar 

  107. Sternlicht MD, Bissell MJ, Werb Z. The matrix metalloproteinase stromelysin-1 acts as a natural mammary tumor promoter. Oncogene 2000;19:1102–13.

    Article  PubMed  CAS  Google Scholar 

  108. Rudolph-Owen LA, Chan R, Muller WJ, Matrisian LM. The matrix metalloproteinase matrilysin influences early-stage mammary tumorigenesis. Cancer Res 1998;58:5500–6.

    PubMed  CAS  Google Scholar 

  109. Hulboy DL, Gautam S, Fingleton B, Matrisian LM. The influence of matrix metalloproteinase-7 on early mammary tumorigenesis in the multiple intestinal neoplasia mouse. Oncol Rep 2004;12:13–7.

    PubMed  CAS  Google Scholar 

  110. Ha HY, Moon HB, Nam MS, Lee JW, Ryoo ZY, Lee TH, et al. Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. Cancer Res 2001;61:984–90.

    PubMed  CAS  Google Scholar 

  111. Soulie P, Carrozzino F, Pepper MS, Strongin AY, Poupon MF, Montesano R. Membrane-type-1 matrix metalloproteinase confers tumorigenicity on nonmalignant epithelial cells. Oncogene 2005;24:1689–97.

    Article  PubMed  CAS  Google Scholar 

  112. Cockett MI, Murphy G, Birch ML, O’Connell JP, Crabbe T, Millican AT, et al. Matrix metalloproteinases and metastatic cancer. Biochem Soc Symp 1998;63:295–313.

    PubMed  CAS  Google Scholar 

  113. Llorens A, Vinyals A, Alia P, Lopez-Barcons L, Gonzalez-Garrigues M, Fabra A. Metastatic ability of MXT mouse mammary subpopulations correlates with clonal expression and/or membrane-association of gelatinase A. Mol Carcinog 1997;19:54–66.

    Article  PubMed  CAS  Google Scholar 

  114. Kupferman ME, Fini ME, Muller WJ, Weber R, Cheng Y, Muschel RJ. Matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. Am J Pathol 2000;157:1777–83.

    PubMed  CAS  Google Scholar 

  115. Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 1998;58:1048–51.

    PubMed  CAS  Google Scholar 

  116. Itoh T, Tanioka M, Matsuda H, Nishimoto H, Yoshioka T, Suzuki R, et al. Experimental metastasis is suppressed in MMP-9-deficient mice. Clin Exp Metastasis 1999;17:177–81.

    Article  PubMed  CAS  Google Scholar 

  117. Hua J, Muschel RJ. Inhibition of matrix metalloproteinase 9 expression by a ribozyme blocks metastasis in a rat sarcoma model system. Cancer Res 1996;56:5279–84.

    PubMed  CAS  Google Scholar 

  118. Sehgal G, Hua J, Bernhard EJ, Sehgal I, Thompson TC, Muschel RJ. Requirement for matrix metalloproteinase-9 (gelatinase B) expression in metastasis by murine prostate carcinoma. Am J Pathol 1998;152:591–6.

    PubMed  CAS  Google Scholar 

  119. Hofmann UB, Eggert AA, Blass K, Brocker EB, Becker JC. Expression of matrix metalloproteinases in the microenvironment of spontaneous and experimental melanoma metastases reflects the requirements for tumor formation. Cancer Res 2003;63:8221–5.

    PubMed  CAS  Google Scholar 

  120. Dalberg K, Eriksson E, Enberg U, Kjellman M, Backdahl M. Gelatinase A, membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: correlation with invasive growth of breast cancer. World J Surg 2000;24:334–40.

    Article  PubMed  CAS  Google Scholar 

  121. Brummer O, Athar S, Riethdorf L, Loning T, Herbst H. Matrix-metalloproteinases 1, 2, and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions: an in situ hybridization study. Virchows Arch 1999;435:566–73.

    Article  PubMed  CAS  Google Scholar 

  122. Chen WT, Wang JY. Specialized surface protrusions of invasive cells, invadopodia and lamellipodia, have differential MT1-MMP, MMP-2, and TIMP-2 localization. Ann N Y Acad Sci 1999;878:361–71.

    Article  PubMed  CAS  Google Scholar 

  123. Bourguignon LY, Gunja-Smith Z, Iida N, Zhu HB, Young LJ, Muller WJ, et al. CD44v(3,8-10) is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells. J Cell Physiol 1998;176:206–15.

    Article  PubMed  CAS  Google Scholar 

  124. Lynch CC, Matrisian LM. Matrix metalloproteinases in tumor–host cell communication. Differentiation 2002;70:561–73.

    Article  PubMed  CAS  Google Scholar 

  125. Basset P, Bellocq JP, Wolf C, Stoll I, Hutin P, Limacher JM, et al. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature 1990;348:699–704.

    Article  PubMed  CAS  Google Scholar 

  126. Heppner KJ, Matrisian LM, Jensen RA, Rodgers WH. Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol 1996;149:273–82.

    PubMed  CAS  Google Scholar 

  127. Stuelten CH, DaCosta Byfield S, Arany PR, Karpova TS, Stetler-Stevenson WG, Roberts AB. Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-alpha and TGF-beta. J Cell Sci 2005;118:2143–53.

    Article  PubMed  CAS  Google Scholar 

  128. Boire A, Covic L, Agarwal A, Jacques S, Sherifi S, Kuliopulos A. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 2005;120:303–13.

    Article  PubMed  CAS  Google Scholar 

  129. Benaud C, Dickson RB, Thompson EW. Roles of the matrix metalloproteinases in mammary gland development and cancer. Breast Cancer Res Treat 1998;50:97–116.

    Article  PubMed  CAS  Google Scholar 

  130. Duffy MJ, Maguire TM, Hill A, McDermott E, O’Higgins N. Metalloproteinases: role in breast carcinogenesis, invasion and metastasis. Breast Cancer Res 2000;2:252–7.

    Article  PubMed  CAS  Google Scholar 

  131. Stetler-Stevenson WG. Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J Clin Invest 1999;103:1237–41.

    Article  PubMed  CAS  Google Scholar 

  132. Xu J, Rodriguez D, Petitclerc E, Kim JJ, Hangai M, Moon YS, et al. Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo. J Cell Biol 2001;154:1069–79.

    Article  PubMed  CAS  Google Scholar 

  133. Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2000;2:737–44.

    Article  PubMed  CAS  Google Scholar 

  134. Dong Z, Kumar R, Yang X, Fidler IJ. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell 1997;88:801–10.

    Article  PubMed  CAS  Google Scholar 

  135. Ferreras M, Felbor U, Lenhard T, Olsen BR, Delaisse J. Generation and degradation of human endostatin proteins by various proteinases. FEBS Lett 2000;486:247–51.

    Article  PubMed  CAS  Google Scholar 

  136. Stamenkovic I. Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol 2000;10:415–33.

    Article  PubMed  CAS  Google Scholar 

  137. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2002;2:161–74.

    Article  PubMed  CAS  Google Scholar 

  138. Folgueras AR, Pendas AM, Sanchez LM, Lopez-Otin C. Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. Int J Dev Biol 2004;48:411–24.

    Article  PubMed  CAS  Google Scholar 

  139. Overall CM, Kleifeld O. Towards third generation matrix metalloproteinase inhibitors for cancer therapy. Br J Cancer 2006;94:941–6.

    Article  PubMed  CAS  Google Scholar 

  140. White JM. ADAMs: modulators of cell–cell and cell–matrix interactions. Curr Opin Cell Biol 2003;15:598–606.

    Article  PubMed  CAS  Google Scholar 

  141. DeClerck YA. Interactions between tumour cells and stromal cells and proteolytic modification of the extracellular matrix by metalloproteinases in cancer. Eur J Cancer 2000;36:1258–68.

    Article  PubMed  CAS  Google Scholar 

  142. Tousseyn T, Jorissen E, Reiss K, Hartmann D. (Make) stick and cut loose-disintegrin metalloproteases in development and disease. Birth Defects Res C Embryo Today 2006;78:24–46.

    Article  PubMed  CAS  Google Scholar 

  143. Lendeckel U, Kohl J, Arndt M, Carl-McGrath S, Donat H, Rocken C. Increased expression of ADAM family members in human breast cancer and breast cancer cell lines. J Cancer Res Clin Oncol 2005;131:41–8.

    Article  PubMed  CAS  Google Scholar 

  144. O’Shea C, McKie N, Buggy Y, Duggan C, Hill AD, McDermott E, et al. Expression of ADAM-9 mRNA and protein in human breast cancer. Int J Cancer 2003;105:754–61.

    Article  PubMed  CAS  Google Scholar 

  145. Borrell-Pages M, Rojo F, Albanell J, Baselga J, Arribas J. TACE is required for the activation of the EGFR by TGF-alpha in tumors. EMBO J 2003;22:1114–24.

    Article  PubMed  CAS  Google Scholar 

  146. Kveiborg M, Frohlich C, Albrechtsen R, Tischler V, Dietrich N, Holck P, et al. A role for ADAM12 in breast tumor progression and stromal cell apoptosis. Cancer Res 2005;65:4754–61.

    Article  PubMed  CAS  Google Scholar 

  147. Roy R, Wewer UM, Zurakowski D, Pories SE, Moses MA. ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage. J Biol Chem 2004;279:51323–30.

    Article  PubMed  CAS  Google Scholar 

  148. Duffy MJ, Maguire TM, McDermott EW, O’Higgins N. Urokinase plasminogen activator: a prognostic marker in multiple types of cancer. J Surg Oncol 1999;71:130–5.

    Article  PubMed  CAS  Google Scholar 

  149. Fisher JL, Field CL, Zhou H, Harris TL, Henderson MA, Choong PF. Urokinase plasminogen activator system gene expression is increased in human breast carcinoma and its bone metastases—a comparison of normal breast tissue, non-invasive and invasive carcinoma and osseous metastases. Breast Cancer Res Treat 2000;61:1–12.

    Article  PubMed  CAS  Google Scholar 

  150. Stephens RW, Brunner N, Janicke F, Schmitt M. The urokinase plasminogen activator system as a target for prognostic studies in breast cancer. Breast Cancer Res Treat 1998;52:99–111.

    Article  PubMed  CAS  Google Scholar 

  151. Duffy MJ. Urokinase-type plasminogen activator: a potent marker of metastatic potential in human cancers. Biochem Soc Trans 2002;30:207–10.

    Article  PubMed  CAS  Google Scholar 

  152. Han B, Nakamura M, Mori I, Nakamura Y, Kakudo K. Urokinase-type plasminogen activator system and breast cancer (Review). Oncol Rep 2005;14:105–12.

    PubMed  CAS  Google Scholar 

  153. Pyke C, Graem N, Ralfkiaer E, Ronne E, Hoyer-Hansen G, Brunner N, et al. Receptor for urokinase is present in tumor-associated macrophages in ductal breast carcinoma. Cancer Res 1993;53:1911–5.

    PubMed  CAS  Google Scholar 

  154. Umeda T, Eguchi Y, Okino K, Kodama M, Hattori T. Cellular localization of urokinase-type plasminogen activator, its inhibitors, and their mRNAs in breast cancer tissues. J Pathol 1997;183:388–97.

    Article  PubMed  CAS  Google Scholar 

  155. Nielsen BS, Sehested M, Duun S, Rank F, Timshel S, Rygaard J, et al. Urokinase plasminogen activator is localized in stromal cells in ductal breast cancer. Lab Invest 2001;81:1485–501.

    PubMed  CAS  Google Scholar 

  156. Hildenbrand R, Arens N. Protein and mRNA expression of uPAR and PAI-1 in myoepithelial cells of early breast cancer lesions and normal breast tissue. Br J Cancer 2004;91:564–71.

    Article  PubMed  CAS  Google Scholar 

  157. Elenbaas B, Weinberg RA. Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation. Exp Cell Res 2001;264:169–84.

    Article  PubMed  CAS  Google Scholar 

  158. Sieuwerts AM, Klijn JG, Henzen-Logmans SC, Foekens JA. Cytokine-regulated urokinase-type-plasminogen-activator (uPA) production by human breast fibroblasts in vitro. Breast Cancer Res Treat 1999;55:9–20.

    Article  PubMed  CAS  Google Scholar 

  159. Frandsen TL, Holst-Hansen C, Nielsen BS, Christensen IJ, Nyengaard JR, Carmeliet P, et al. Direct evidence of the importance of stromal urokinase plasminogen activator (uPA) in the growth of an experimental human breast cancer using a combined uPA gene-disrupted and immunodeficient xenograft model. Cancer Res 2001;61:532–7.

    PubMed  CAS  Google Scholar 

  160. Almholt K, Lund LR, Rygaard J, Nielsen BS, Dano K, Romer J, et al. Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice. Int J Cancer 2005;113:525–32.

    Article  PubMed  CAS  Google Scholar 

  161. Guo Y, Higazi AA, Arakelian A, Sachais BS, Cines D, Goldfarb RH, et al. A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo. FASEB J 2000;14:1400–10.

    Article  PubMed  CAS  Google Scholar 

  162. Rabbani SA, Gladu J. Urokinase receptor antibody can reduce tumor volume and detect the presence of occult tumor metastases in vivo. Cancer Res 2002;62:2390–7.

    PubMed  CAS  Google Scholar 

  163. Decock J, Paridaens R, Cufer T. Proteases and metastasis: clinical relevance nowadays? Curr Opin Oncol 2005;17:545–50.

    Article  PubMed  CAS  Google Scholar 

  164. Foekens JA, Look MP, Bolt-de Vries J, Meijer-van Gelder ME, van Putten WL, Klijn JG. Cathepsin-D in primary breast cancer: prognostic evaluation involving 2810 patients. Br J Cancer 1999;79:300–7.

    Article  PubMed  CAS  Google Scholar 

  165. Westley BR, May FE. Prognostic value of cathepsin D in breast cancer. Br J Cancer 1999;79:189–90.

    PubMed  CAS  Google Scholar 

  166. Lah TT, Cercek M, Blejec A, Kos J, Gorodetsky E, Somers R, et al. Cathepsin B, a prognostic indicator in lymph node-negative breast carcinoma patients: comparison with cathepsin D, cathepsin L, and other clinical indicators. Clin Cancer Res 2000;6:578–84.

    PubMed  CAS  Google Scholar 

  167. Rochefort H, Garcia M, Glondu M, Laurent V, Liaudet E, Rey JM, et al. Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview. Clin Chim Acta 2000;291:157–70.

    Article  PubMed  CAS  Google Scholar 

  168. Levicar N, Kos J, Blejec A, Golouh R, Vrhovec I, Frkovic-Grazio S, et al. Comparison of potential biological markers cathepsin B, cathepsin L, stefin A and stefin B with urokinase and plasminogen activator inhibitor-1 and clinicopathological data of breast carcinoma patients. Cancer Detect Prev 2002;26:42–9.

    Article  PubMed  CAS  Google Scholar 

  169. Fusek M, Vetvicka V. Mitogenic function of human procathepsin D: the role of the propeptide. Biochem J 1994;303(Pt 3):775–80.

    PubMed  CAS  Google Scholar 

  170. Vetvicka V, Vetvickova J, Fusek M. Anti-human procathepsin D activation peptide antibodies inhibit breast cancer development. Breast Cancer Res Treat 1999;57:261–9.

    Article  PubMed  CAS  Google Scholar 

  171. Glondu M, Liaudet-Coopman E, Derocq D, Platet N, Rochefort H, Garcia M. Down-regulation of cathepsin-D expression by antisense gene transfer inhibits tumor growth and experimental lung metastasis of human breast cancer cells. Oncogene 2002;21:5127–34.

    Article  PubMed  CAS  Google Scholar 

  172. Premzl A, Puizdar V, Zavasnik-Bergant V, Kopitar-Jerala N, Lah TT, Katunuma N, et al. Invasion of ras-transformed breast epithelial cells depends on the proteolytic activity of cysteine and aspartic proteinases. Biol Chem 2001;382:853–7.

    Article  PubMed  CAS  Google Scholar 

  173. Berchem G, Glondu M, Gleizes M, Brouillet JP, Vignon F, Garcia M, et al. Cathepsin-D affects multiple tumor progression steps in vivo: proliferation, angiogenesis and apoptosis. Oncogene 2002;21:5951–55.

    Article  PubMed  CAS  Google Scholar 

  174. Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, et al. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev 2006;20:543–56.

    Article  PubMed  CAS  Google Scholar 

  175. Liaudet-Coopman E, Beaujouin M, Derocq D, Garcia M, Glondu-Lassis M, Laurent-Matha V, et al. Cathepsin D: newly discovered functions of a long-standing aspartic protease in cancer and apoptosis. Cancer Lett 2006;237:167–79.

    Article  PubMed  CAS  Google Scholar 

  176. Benes P, Vashishta A, Saraswat-Ohri S, Fusek M, Pospisilova S, Tichy B, et al. Effect of procathepsin D activation peptide on gene expression of breast cancer cells. Cancer Lett 2006;239:46–54.

    Article  PubMed  CAS  Google Scholar 

  177. Nomura T, Katunuma N. Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells. J Med Invest 2005;52:1–9.

    Article  PubMed  Google Scholar 

  178. Rich JN, Shi Q, Hjelmeland M, Cummings TJ, Kuan CT, Bigner DD, et al. Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model. J Biol Chem 2003;278:15951–7.

    Article  PubMed  CAS  Google Scholar 

  179. Ausprunk DH, Knighton DR, Folkman J. Differentiation of vascular endothelium in the chick chorioallantois: a structural and autoradiographic study. Dev Biol 1974;38:237–48.

    Article  PubMed  CAS  Google Scholar 

  180. Ribatti D, Vacca A. Models for studying angiogenesis in vivo. Int J Biol Markers 1999;14:207–13.

    PubMed  CAS  Google Scholar 

  181. Chambers AF, MacDonald IC, Schmidt EE, Koop S, Morris VL, Khokha R, et al. Steps in tumor metastasis: new concepts from intravital videomicroscopy. Cancer Metastasis Rev 1995;14:279–301.

    Article  PubMed  CAS  Google Scholar 

  182. Vajkoczy P, Ullrich A, Menger MD. Intravital fluorescence videomicroscopy to study tumor angiogenesis and microcirculation. Neoplasia 2000;2:53–61.

    Article  PubMed  CAS  Google Scholar 

  183. Thompson SC. The colony forming efficiency of single cells and cell aggregates from a spontaneous mouse mammary tumour using the lung colony assay. Br J Cancer 1974;30:332–6.

    PubMed  CAS  Google Scholar 

  184. Francis JL, Amirkhosravi A. Effect of antihemostatic agents on experimental tumor dissemination. Semin Thromb Hemost 2002;28:29–38.

    Article  PubMed  CAS  Google Scholar 

  185. Amirkhosravi A, Mousa SA, Amaya M, Blaydes S, Desai H, Meyer T, et al. Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb/IIIa antagonist XV454. Thromb Haemost 2003;90:549–54.

    PubMed  CAS  Google Scholar 

  186. Amirkhosravi A, Mousa SA, Amaya M, Francis JL. Antimetastatic effect of tinzaparin, a low-molecular-weight heparin. J Thromb Haemost 2003;1:1972–6.

    Article  PubMed  CAS  Google Scholar 

  187. Gasic GJ. Role of plasma, platelets, and endothelial cells in tumor metastasis. Cancer Metastasis Rev 1984;3:99–114.

    Article  PubMed  CAS  Google Scholar 

  188. Glinskii OV, Huxley VH, Glinsky GV, Pienta KJ, Raz A, Glinsky VV. Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs. Neoplasia 2005;7:522–7.

    Article  PubMed  CAS  Google Scholar 

  189. Massoud TF, Gambhir SS. Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev 2003;17:545–80.

    Article  PubMed  CAS  Google Scholar 

  190. Weissleder R. Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2002;2:11–8.

    Article  PubMed  CAS  Google Scholar 

  191. Bremer C, Tung CH, Weissleder R. In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med 2001;7:743–8.

    Article  PubMed  CAS  Google Scholar 

  192. Bremer C, Bredow S, Mahmood U, Weissleder R, Tung CH. Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model. Radiology 2001;221:523–9.

    Article  PubMed  CAS  Google Scholar 

  193. Bremer C, Tung CH, Bogdanov A, Jr., Weissleder R. Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypes. Radiology 2002;222:814–8.

    Article  PubMed  Google Scholar 

  194. Bogdanov AA, Jr., Lin CP, Simonova M, Matuszewski L, Weissleder R. Cellular activation of the self-quenched fluorescent reporter probe in tumor microenvironment. Neoplasia 2002;4:228–36.

    Article  PubMed  CAS  Google Scholar 

  195. Weissleder R, Tung CH, Mahmood U, Bogdanov A, Jr. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999;17:375–8.

    Article  PubMed  CAS  Google Scholar 

  196. Yang M, Li L, Jiang P, Moossa AR, Penman S, Hoffman RM. Dual-color fluorescence imaging distinguishes tumor cells from induced host angiogenic vessels and stromal cells. Proc Natl Acad Sci U S A 2003;100:14259–62.

    Article  PubMed  CAS  Google Scholar 

  197. Laxman B, Hall DE, Bhojani MS, Hamstra DA, Chenevert TL, Ross BD, et al. Noninvasive real-time imaging of apoptosis. Proc Natl Acad Sci U S A 2002;99:16551–5.

    Article  PubMed  CAS  Google Scholar 

  198. Lyons SK. Advances in imaging mouse tumour models in vivo. J Pathol 2005;205:194–205.

    Article  PubMed  CAS  Google Scholar 

  199. Bhujwalla ZM, Artemov D, Ballesteros P, Cerdan S, Gillies RJ, Solaiyappan M. Combined vascular and extracellular pH imaging of solid tumors. NMR Biomed 2002;15:114–9.

    Article  PubMed  CAS  Google Scholar 

  200. Fukumura D, Xavier R, Sugiura T, Chen Y, Park EC, Lu N, et al. Tumor induction of VEGF promoter activity in stromal cells. Cell 1998;94:715–25.

    Article  PubMed  CAS  Google Scholar 

  201. Robey IF, Lien AD, Welsh SJ, Baggett BK, Gillies RJ. Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors. Neoplasia 2005;7:324–30.

    Article  PubMed  CAS  Google Scholar 

  202. Miller KD, Miller M, Mehrotra S, Agarwal B, Mock BH, Zheng QH, et al. A physiologic imaging pilot study of breast cancer treated with AZD2171. Clin Cancer Res 2006;12:281–8.

    Article  PubMed  CAS  Google Scholar 

  203. Dadiani M, Kalchenko V, Yosepovich A, Margalit R, Hassid Y, Degani H, et al. Real-time Imaging of Lymphogenic Metastasis in Orthotopic Human Breast Cancer. Cancer Res 2006;66:8037–41.

    Article  PubMed  CAS  Google Scholar 

  204. Carlson AL, Hoffmeyer MR, Wall KM, Baugher PJ, Richards-Kortum R, Dharmawardhane SF. In situ analysis of breast cancer progression in murine models using a macroscopic fluorescence imaging system. Lasers Surg Med 2006.

  205. Winnard PT, Jr., Kluth JB, Raman V. Noninvasive optical tracking of red fluorescent protein-expressing cancer cells in a model of metastatic breast cancer. Neoplasia 2006;8:796–806.

    Article  PubMed  CAS  Google Scholar 

  206. Wetterwald A, van der Pluijm G, Que I, Sijmons B, Buijs J, Karperien M, et al. Optical imaging of cancer metastasis to bone marrow: a mouse model of minimal residual disease. Am J Pathol 2002;160:1143–53.

    PubMed  Google Scholar 

  207. Jenkins DE, Hornig YS, Oei Y, Dusich J, Purchio T. Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice. Breast Cancer Res 2005;7:R444–54.

    Article  PubMed  CAS  Google Scholar 

  208. Heyn C, Ronald JA, Ramadan SS, Snir JA, Barry AM, MacKenzie LT, et al. In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain. Magn Reson Med 2006;56:1001–10.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by grants HD050067 (AEV), CA98371, and CA105490 from the NIH, as well as U.S. Army Breast Cancer Research Program grant W81XWH-05-1-0405, and PDF88706 (S.J.B) from the Susan G. Komen Foundation.

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Vernon, A.E., Bakewell, S.J. & Chodosh, L.A. Deciphering the molecular basis of breast cancer metastasis with mouse models. Rev Endocr Metab Disord 8, 199–213 (2007). https://doi.org/10.1007/s11154-007-9041-5

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