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Microenvironmental Influence on Breast Cancer Dormancy and Metastasis

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Tumor Dormancy, Quiescence, and Senescence, Volume 1

Part of the book series: Tumor Dormancy and Cellular Quiescence and Senescence ((DOQU,volume 1))

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Abstract

Breast cancer remains a serious public health issue; this despite early diagnosis and aggressive treatment. This chapter discusses the different aspects that are contributors in the evasion of cancer. The review discusses the emerging role of cancer stem cells in dormancy. Included in the discussion are studies on mesenchymal stem cells as protection for the cancer cells from immune clearance. We reviewed the role of hormones and the intracellular pathways in metastasis. Overall, this review provides a ‘snapshot’ of breast cancer subset in dormancy and immune evasion.

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Abbreviations

ABC:

ATP-binding cassette

BC:

breast cancer

BCC:

breast cancer cell

CCL5:

chemokine C-C ligand 5

CSC:

cancer stem cells

CSF:

colony stimulating factor

CTL:

cytotoxic T lymphocyte

CTLA-4:

cytotoxic T lymphocyte antigen 4

CXCL12:

C-X-C motif chemokine 12

CXCR4:

C-X-C chemokine receptor type 4

CTC:

circulating tumor cells

EMT:

epithelial to mesenchymal transition

FOXP3:

forkhead lineage-specific transcription factor

GJIC:

gap junctional intercellular communi­cation

miRNA:

microRNA

MSC:

mesenchymal stem cell

NK:

natural killer

NKT:

natural killer T cells

NOD:

non-obese diabetic

PTHrP:

parathyroid hormone-related protein

RANK:

receptor activator of nuclear factor kappa-B

RANKL:

receptor activator of nuclear factor kappa-B ligand

SDF-1:

stromal cell-derived factor 1

SCID:

severe combined immunodeficiency

TGF-β:

transforming growth factor beta

Tregs :

regulatory T cells

VEGF:

vascular endothelial growth factor

References

  • Al-Hajj M, Wicha MS, Benito-Hernandez A, Morisson SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100(7):3983–3988

    Article  PubMed  CAS  Google Scholar 

  • Azuma T, Takahashi T, Kunisato A, Kitamura T, Hirai H (2003) Human CD4+ CD25+ regulatory T cells suppress NKT cell functions. Cancer Res 63(15):4516–4520

    PubMed  CAS  Google Scholar 

  • Bendre M, Gaddy D, Nicholas RW, Suva LJ (2003) Breast cancer metastasis to bone: it is not all about PTHrP. Clin Orthop Relat Res 415(Suppl): S39–S45

    Google Scholar 

  • Castano Z, Tracy K, McAllister SS (2011) The tumor macroenvironment and systemic regulation of breast cancer progression. Int J Dev Biol 55:889–897

    Article  PubMed  Google Scholar 

  • Chaffer CL, Thompson EW, Williams ED (2007) Mesenchymal to epithelial transition in development and disease. Cells Tissues Organs 185(1–3):7–19

    Article  PubMed  Google Scholar 

  • Chao K-C, Yang H-T, Weng MW (2011) Human umbilical cord mesenchymal stem cells suppress breast cancer tumorigenesis through direct cell-cell contact and internalization. J Cell Mole Med 16:1803–1815

    Google Scholar 

  • Cho JA, Park H, Lim EH, Lee KW (2012) Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal stem cells into myofibroblast-like cells. Int J Oncol 40(1):130–138

    PubMed  CAS  Google Scholar 

  • Corcoran KE, Trzaska KA, Fernandes H, Bryan M, Taborga M, Srinivas V, Packman K, Patel PS, Rameshwar P (2008) Mesenchymal stem cells in early entry of breast cancer into bone marrow. PLoS One 3(6):e2563

    Article  PubMed  Google Scholar 

  • Dohadwala M, Heinrich GE, Luo J, Lau O, Shih H, Munaim Q, Lee G, Hong L, Lai C, Abemayor E, Fishbein MC, Elashoff DA, Dubinett SM, St. John MA (2010) The role of ZEB1 in the inflammation-induced promotion of EMT in HNSCC. Otolaryngol Head Neck Surg 142(5):753–759

    Article  PubMed  Google Scholar 

  • Fidler IJ (1973) Selection of successive tumour lines for metastasis. Nat New Biol 242(118):148–149

    PubMed  CAS  Google Scholar 

  • Fidler IJ, Gruys E, Cifone MA, Barnes Z, Bucana C (1981) Demonstration of multiple phenotypic diversity in a murine melanoma of recent origin. J Natl Cancer Inst 67(4):947–956

    PubMed  CAS  Google Scholar 

  • Garcia-Olmo D, Garcia-Arranz M, Herreros D, Pascual I, Peiro C, Rodriguez-Montes JA (2005) A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 48(7):1416–1426

    Article  PubMed  Google Scholar 

  • Gehmert S, Gehmert S, Bai X, Klein S, Ortmann O, Prantl L (2011) Limitation of in vivo models investigating angiogenesis in breast cancer. Clin Hemorheol Microcircul 49(1):519–526

    Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70

    Article  PubMed  CAS  Google Scholar 

  • Holmgren L, O’Reilly MS, Folkman J (1995) Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1(2):149–153

    Article  PubMed  CAS  Google Scholar 

  • Ida R (2006) Immune modulation by mesenchymal stem cells. Exp Cell Res 312(12):2169–2179

    Article  Google Scholar 

  • Kiel MJ, Morrison SJ (2008) Uncertainty in the niches that maintain haematopoietic stem cells. Nat Rev Immunol 8(4):290–301

    Article  PubMed  CAS  Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caliguri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648

    Article  PubMed  CAS  Google Scholar 

  • Lim PK, Bliss SA, Patel SA, Taborga M, Dave MA, Gregory LA, Gregory SJ, Bryan M, Patel PS, Rameshwar P (2011) Gap junction-mediated import of MicroRNA from bone marrow stromal cells can elicit cell cycle quiescence in breast cancer cells. Cancer Res 71(5):1550–1560

    Article  PubMed  CAS  Google Scholar 

  • Mishra PJ, Mishra PJ, Humeniuk R, Medina DJ, Alexe G, Mesirov JP, Ganesan S, Glod JW, Banerjee D (2008) Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res 68(11):4331–4339

    Article  PubMed  CAS  Google Scholar 

  • Moharita AL, Taborga M, Corcoran KE, Bryan M, Patel PS, Rameshwar P (2006) SDF-1alpha regulation in breast cancer cells contacting bone marrow stroma is critical for normal hematopoiesis. Blood 108(10):3245–3252

    Article  PubMed  CAS  Google Scholar 

  • Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 1:571–573

    Article  Google Scholar 

  • Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P (2010) Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-β. J Immunol 184(10):5885–5894

    Article  PubMed  CAS  Google Scholar 

  • Pelger RC, Hamdy NA, Zwinderman AH, Papapoulos SE, Lycklama a Nijeholt AA (1998) Effects of the bisphosphonate olpadronate in patients with carcinoma of the prostate metastatic to the skeleton. Bone 22(4):403–408

    Article  PubMed  Google Scholar 

  • Powell GJ, Southby J, Danks JA, Stillwell RG, Hayman JA, Henderson MA, Bennett RC, Martin TJ (1991) Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res 51(11):3059–3061

    PubMed  CAS  Google Scholar 

  • Rameshwar P, Oh HS, Yook C, Gascon P, Chang VT (2003) Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis. Acta Haematol 109(1):1–10

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi S (2004) Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22(1):531–562

    Article  PubMed  CAS  Google Scholar 

  • Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat M, Wu L, Lindeman JH, Visvader E (2006) Generation of a functional mammary gland from a single stem cell. Nature 439(7072):84–88

    Article  PubMed  CAS  Google Scholar 

  • Stuelten CH, Busch JI, Tang B, Flanders KC, Oshima A, Sutton E, Karpova TS, Roberts AB, Wakefield LM, Niederhuber JE (2010) Transient tumor-fibroblast interactions increase tumor cell malignancy by a TGF-β mediated mechanism in a mouse xenograft model of breast cancer. PLoS One 5(3):e9832

    Article  PubMed  Google Scholar 

  • Talmadge JE (2007) Clonal selection of metastasis within the life history of a tumor. Cancer Res 67(24):11471–11475

    Article  PubMed  CAS  Google Scholar 

  • Tan W, Zhang W, Strasner A, Grivennikov S, Cheng JQ, Hoffman RM, Karin M (2011) Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 470(7335):548–553

    Article  PubMed  CAS  Google Scholar 

  • Tarin D, Price JE, Kettlewell MG, Souter RG, Vass AC, Crossley B (1984) Mechanisms of human tumor metastasis studied in patients with peritoneovenous shunts. Cancer Res 44(8):3584–3592

    PubMed  CAS  Google Scholar 

  • Van Der Pluijm G, Sijmons B, Vloedgraven H, Deckers M, Papapoulos S, Lowik C (2001) Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases. J Bone Miner Res 16(6):1077–1091

    Article  PubMed  Google Scholar 

  • Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorentino BP (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7(9):1028–1034

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. University of Medicine and Dentistry of New Jersey, New Jersey Medical School, MSB, Room E-579, 185 South Orange Avenue, Newark, NJ, 07103, USA

    George R. Nahas, Jacqueline M. Park & Pranela Rameshwar

Authors
  1. George R. Nahas
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  2. Jacqueline M. Park
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  3. Pranela Rameshwar
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Correspondence to Pranela Rameshwar .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Nahas, G.R., Park, J.M., Rameshwar, P. (2013). Microenvironmental Influence on Breast Cancer Dormancy and Metastasis. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 1. Tumor Dormancy and Cellular Quiescence and Senescence, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5958-9_3

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