Advertisement

Protocols for Studies on Stromal Cells in Prostate Cancer

  • Damien A. LeachEmail author
  • Grant Buchanan
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1786)

Abstract

Interactions between tumor cells and fibroblasts play a pivotal role in cancer development and progression. Indeed, the paracrine communication between these two cell types is known to have physiological effects that alter carcinogenic and metastatic potential. An often overlooked player in these interactions is the involvement of the extracellular matrix (ECM). The network of ECM proteins secreted from fibroblasts is reportedly altered with cancer initiation and progression, and in several cases has been associated with patient outcome. The androgen receptor (AR) is one such example and has been shown to be a dynamic and inducible regulator of ECM production. Contemporary assessment of dynamic multicellular interactions leading to cancer initiation and progression necessitates 3D in vitro modeling to better mimic the in vivo environment. In the current chapter, we describe some simple approaches to generate 3D models of fibroblast-produced ECM, how hormone manipulation of fibroblasts can lead to production of different ECMs, and how these ECM models can be used to test processes implicated in cancer progression and metastasis.

Key words

Fibroblasts ECM 3D-modeling Invasion Motility Adhesion Proteomics Cell culture 

References

  1. 1.
    Tuxhorn JA, Ayala GE, Smith MJ, Smith VC, Dang TD, Rowley DR (2002) Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res 8(9):2912–2923PubMedGoogle Scholar
  2. 2.
    Palumbo A Jr, Ferreira LB, Reis de Souza PA et al (2012) Extracellular matrix secreted by reactive stroma is a main inducer of pro-tumorigenic features on LNCaP prostate cancer cells. Cancer Lett 321(1):55–64CrossRefPubMedGoogle Scholar
  3. 3.
    Hynes RO (2009) The extracellular matrix: not just pretty fibrils. Science 326(5957):1216–1219CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kim SH, Turnbull J, Guimond S (2011) Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol 209(2):139–151CrossRefPubMedGoogle Scholar
  5. 5.
    Vlodavsky I, Korner G, Ishai-Michaeli R, Bashkin P, Bar-Shavit R, Fuks Z (1990) Extracellular matrix-resident growth factors and enzymes: possible involvement in tumor metastasis and angiogenesis. Cancer Metastasis Rev 9(3):203–226CrossRefPubMedGoogle Scholar
  6. 6.
    Stewart DA, Cooper CR, Sikes RA (2004) Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer. Reprod Biol Endocrinol 2:2CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Paszek MJ, Zahir N, Johnson KR et al (2005) Tensional homeostasis and the malignant phenotype. Cancer Cell 8(3):241–254CrossRefGoogle Scholar
  8. 8.
    Sahai E (2005) Mechanisms of cancer cell invasion. Curr Opin Genet Dev 15(1):87–96CrossRefPubMedGoogle Scholar
  9. 9.
    Carey SP, Kraning-Rush CM, Williams RM, Reinhart-King CA (2012) Biophysical control of invasive tumor cell behavior by extracellular matrix microarchitecture. Biomaterials 33(16):4157–4165CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Nguyen-Ngoc KV, Cheung KJ, Brenot A, Shamir ER, Gray RS, Hines WC, Yaswen P, Werb Z, Ewald AJ (2012) ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. Proc Natl Acad Sci U S A 109(39):E2595–E2604CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mohler JL, Chen Y, Hamil K, Hall SH, Cidlowski JA, Wilson EM, French FS, Sar M (1996) Androgen and glucocorticoid receptors in the stroma and epithelium of prostatic hyperplasia and carcinoma. Clin Cancer Res 2(5):889–895PubMedGoogle Scholar
  12. 12.
    Olapade-Olaopa EO, MacKay M, Taub NA, Sandhu DP, Terry TR, Habib FK (1999) Malignant transformation of human prostatic epithelium is associated with the loss of androgen receptor immunoreactivity in the surrounding stroma. Clin Cancer Res 5(3):569–576PubMedGoogle Scholar
  13. 13.
    Henshall SM, Quinn DI, Lee CS et al (2001) Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer. Cancer Res 61(2):423–427PubMedGoogle Scholar
  14. 14.
    Ricciardelli C, Choong CS, Buchanan G, Vivekanandan S, Neufing P, Stahl J, Marshall VR, Horsfall DJ, Tilley WD (2005) Androgen receptor levels in prostate cancer epithelial and peritumoral stromal cells identify non-organ confined disease. Prostate 63(1):19–28CrossRefPubMedGoogle Scholar
  15. 15.
    Li Y, Li CX, Ye H et al (2008) Decrease in stromal androgen receptor associates with androgen-independent disease and promotes prostate cancer cell proliferation and invasion. J Cell Mol Med 12(6B):2790–2798CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wikstrom P, Marusic J, Stattin P, Bergh A (2009) Low stroma androgen receptor level in normal and tumor prostate tissue is related to poor outcome in prostate cancer patients. Prostate 69(8):799–809CrossRefPubMedGoogle Scholar
  17. 17.
    Leach DA, Need EF, Toivanen R et al (2015) Stromal androgen receptor regulates the composition of the microenvironment to influence prostate cancer outcome. Oncotarget 6(18):16135–16150CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    DeNichilo MO, Shoubridge AJ, Panagopoulos V et al (2016) Peroxidase enzymes regulate collagen biosynthesis and matrix mineralization by cultured human osteoblasts. Calcif Tissue Int 98(3):294–305CrossRefPubMedGoogle Scholar
  19. 19.
    Castello-Cros R, Cukierman E (2009) Stromagenesis during tumorigenesis: characterization of tumor-associated fibroblasts and stroma-derived 3D matrices. Methods Mol Biol 522:275–305CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Han W, Chen S, Yuan W et al (2016) Oriented collagen fibers direct tumor cell intravasation. Proc Natl Acad Sci U S A 113(40):11208–11213CrossRefGoogle Scholar
  21. 21.
    Tozluoglu M, Tournier AL, Jenkins RP, Hooper S, Bates PA, Sahai E (2013) Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions. Nat Cell Biol 15(7):751–762CrossRefPubMedGoogle Scholar
  22. 22.
    Ulrich TA, de Juan Pardo EM, Kumar S (2009) The mechanical rigidity of the extracellular matrix regulates the structure, motility, and proliferation of glioma cells. Cancer Res 69(10):4167–4174CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Wolf K, Te Lindert M, Krause M et al (2013) Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J Cell Biol 201(7):1069–1084CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Ween MP, Hummitzsch K, Rodgers RJ, Oehler MK, Ricciardelli C (2011) Versican induces a pro-metastatic ovarian cancer cell behavior which can be inhibited by small hyaluronan oligosaccharides. Clin Exp Metastasis 28(2):113–125CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Divisions of Medicine and Surgery, The Basil Hetzel Institute for Translational Health ResearchUniversity of AdelaideAdelaideAustralia
  2. 2.Department of Surgery and CancerImperial College LondonLondonUK
  3. 3.Department of Radiation OncologyCanberra Teaching HospitalCanberraAustralia

Personalised recommendations