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Cellular and Molecular Bioengineering

, Volume 7, Issue 3, pp 409–420 | Cite as

Endometriotic Epithelial Cell Response to Macrophage-Secreted Factors is Dependent on Extracellular Matrix Context

  • Kathryn Pollock
  • Taylor J. Jaraczewski
  • Molly J. Carroll
  • Dan I. Lebovic
  • Pamela K. Kreeger
Article

Abstract

Endometriosis is a chronic disease in which epithelial and stromal cells that resemble the eutopic endometrium are found in ectopic lesions. In order to examine how microenvironmental factors such as extracellular matrix (ECM) and macrophages influence disease progression, 12Z (an immortalized ectopic epithelial cell line) were cultured on tissue culture plastic or in gels of recombinant basement membrane (rBM) or collagen I. Unlike cells in other conditions, cells in rBM formed multi-cellular structures in a 67 kDa non-integrin laminin receptor (67LR)-dependent manner. To examine the impact of macrophage-secreted factors on cell behavior, 12Z cells on all three substrates were treated with conditioned media from differentiated THP-1 (an immortalized monocytic cell line). Significant proliferation and invasion was observed only with cells cultured in rBM, indicating that ECM cues help dictate cell response to soluble signals. Cells cultured on rBM were then treated with individual cytokines detected in the conditioned media, with increased proliferation observed following exposure to interleukin-8 (CXCL8/IL-8) and both increased proliferation and invasion following treatment with heparin-binding EGF-like growth factor (HB-EGF). This study suggests that rBM gels can be used to induce in vitro lesion formation in order to identify soluble factors that influence proliferation and invasion.

Keywords

Endometriosis 3D culture Heparin-binding EGF-like growth factor (HB-EGF) CXCL8 Basement membrane 

Notes

Acknowledgments

We would like to acknowledge Anthony Desotell and Danielle Bourgeois for help with the ErbB ligand ELISAs, Adriana Rodriguez for assistance with the proliferation experiments, Alex LaPerle for providing the ECM adsorption protocols, and the imaging assistance of the Laboratory for Optical and Computational Instrumentation (LOCI) at the University of Wisconsin-Madison. We gratefully acknowledge Dr. Kristyn Masters and Dr. Brenda Ogle for use of the time-lapse microscope. Funding for this work was provided by NSF CBET-0951613 (P.K.K.), American Cancer Society RSG-13-026-01-CSM (P.K.K.), UW-Madison Graduate Research School Grant (P.K.K.), and a NSF GRFP (M.J.C.).

Conflict of interest

Kathryn Pollock, Taylor Jaraczewski, Molly J. Carroll, and Pamela Kreeger declare that they have no conflicts of interest. Dan Lebovic is part of a multi-center endometriosis trial for AbbVie Pharmaceuticals and has received a contribution from UpToDate, Inc.

Ethical Standards

No human or animal studies were carried out by the authors for this article.

Supplementary material

12195_2014_339_MOESM1_ESM.doc (3.6 mb)
Supplementary material 1 (DOC 3676 kb)

References

  1. 1.
    Aplin, J. D. Endometrial extracellular matrix. In: The Endometrium: Molecular, Cellular, and Clinical Perspectives2nd, edited by J. D. Aplin, A. T. Fazleabas, S. R. Glasser, and L. C. Giudice. Boca Raton, FL: Informa UK Ltd., 2008, pp. 364–378.CrossRefGoogle Scholar
  2. 2.
    Arnold, J. T., D. G. Kaufman, M. Seppala, and B. A. Lessey. Endometrial stromal cells regulate epithelial cell growth in vitro: a new co-culture model. Hum. Reprod. 16:836–845, 2001.CrossRefGoogle Scholar
  3. 3.
    Bacci, M., A. Capobianco, A. Monno, L. Cottone, F. Di Puppo, B. Camisa, M. Mariani, C. Brignole, M. Ponzoni, S. Ferrari, P. Panina-Bordignon, A. A. Manfredi, et al. Macrophages are alternatively activated in patients with endometriosis and required for growth and vascularization of lesions in a mouse model of disease. Am. J. Pathol. 175:547–556, 2009.CrossRefGoogle Scholar
  4. 4.
    Barcellos-Hoff, M. H., J. Aggeler, T. G. Ram, and M. J. Bissell. Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development 105:223–235, 1989.Google Scholar
  5. 5.
    Bauvois, B., and S. Roth. Initial adhesion of murine fibroblasts to collagen and fibronectin occurs by two mechanisms. Cell Biochem. Funct. 5:281–287, 1987.CrossRefGoogle Scholar
  6. 6.
    Beliard, A., J. Donnez, M. Nisolle, and J. M. Foidart. Localization of laminin, fibronectin, E-cadherin, and integrins in endometrium and endometriosis. Fertil. Steril. 67:266–272, 1997.CrossRefGoogle Scholar
  7. 7.
    Bentin-Ley, U., B. Pedersen, S. Lindenberg, J. F. Larsen, L. Hamberger, and T. Horn. Isolation and culture of human endometrial cells in a three-dimensional culture system. J. Reprod. Fertil. 101:327–332, 1994.CrossRefGoogle Scholar
  8. 8.
    Berrier, A. L., and K. M. Yamada. Cell-matrix adhesion. J. Cell. Physiol. 213:565–573, 2007.CrossRefGoogle Scholar
  9. 9.
    Bersinger, N. A., S. von Roten, D. M. Wunder, L. Raio, E. Dreher, and M. D. Mueller. PAPP-A and osteoprotegerin, together with interleukin-8 and RANTES, are elevated in the peritoneal fluid of women with endometriosis. Am. J. Obstet. Gynecol. 195:103–108, 2006.CrossRefGoogle Scholar
  10. 10.
    Brown, X. Q., E. Bartolak-Suki, C. Williams, M. L. Walker, V. M. Weaver, and J. Y. Wong. Effect of substrate stiffness and PDGF on the behavior of vascular smooth muscle cells: implications for atherosclerosis. J. Cell. Physiol. 225:115–122, 2010.CrossRefGoogle Scholar
  11. 11.
    Bulun, S. E. Endometriosis. N. Engl. J. Med. 360:268–279, 2009.CrossRefGoogle Scholar
  12. 12.
    Callister, W. D. Fundamentals of Materials Science and Engineering: An Interactive E-Text. Somerset, NJ: Wiley, 2000.Google Scholar
  13. 13.
    Chacho, K. J., M. S. Chacho, P. J. Andresen, and A. Scommegna. Peritoneal fluid in patients with and without endometriosis: prostanoids and macrophages and their effect on the spermatozoa penetration assay. Am. J. Obstet. Gynecol. 154:1290–1299, 1986.CrossRefGoogle Scholar
  14. 14.
    Chetty, C., T. Khumalo, B. Da Costa Dias, U. Reusch, S. Knackmuss, M. Little, and S. F. Weiss. Anti-LRP/LR specific antibody IgG1-iS18 impedes adhesion and invasion of liver cancer cells. PLoS ONE 9:e96268, 2014.CrossRefGoogle Scholar
  15. 15.
    Classen-Linke, I., M. Kusche, R. Knauthe, and H. M. Beier. Establishment of a human endometrial cell culture system and characterization of its polarized hormone responsive epithelial cells. Cell Tissue Res. 287:171–185, 1997.CrossRefGoogle Scholar
  16. 16.
    Dunselman, G. A., M. G. Hendrix, P. X. Bouckaert, and J. L. Evers. Functional aspects of peritoneal macrophages in endometriosis of women. J. Reprod. Fertil. 82:707–710, 1988.CrossRefGoogle Scholar
  17. 17.
    Elenius, K., S. Paul, G. Allison, J. Sun, and M. Klagsbrun. Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. EMBO J. 16:1268–1278, 1997.CrossRefGoogle Scholar
  18. 18.
    Eyster, K. M., K. A. Hansen, E. Winterton, O. Klinkova, D. Drappeau, and C. J. Mark-Kappeler. Reciprocal communication between endometrial stromal cells and macrophages. Reprod. Sci. 17:809–822, 2010.CrossRefGoogle Scholar
  19. 19.
    Falcone, T., and D. I. Lebovic. Clinical management of endometriosis. Obstet. Gynecol. 118:691–705, 2011.CrossRefGoogle Scholar
  20. 20.
    Fauconnier, A., and C. Chapron. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum. Reprod. Update 11:595–606, 2005.CrossRefGoogle Scholar
  21. 21.
    Giudice, L. C., and L. C. Kao. Endometriosis. Lancet 364:1789–1799, 2004.CrossRefGoogle Scholar
  22. 22.
    Griffith, L. G., and M. A. Swartz. Capturing complex 3D tissue physiology in vitro. Nat. Rev. Mol. Cell Biol. 7:211–224, 2006.CrossRefGoogle Scholar
  23. 23.
    Grinnell, F., C. H. Ho, E. Tamariz, D. J. Lee, and G. Skuta. Dendritic fibroblasts in three-dimensional collagen matrices. Mol. Biol. Cell 14:384–395, 2003.CrossRefGoogle Scholar
  24. 24.
    Grund, E. M., D. Kagan, C. A. Tran, A. Zeitvogel, A. Starzinski-Powitz, S. Nataraja, and S. S. Palmer. Tumor necrosis factor-alpha regulates inflammatory and mesenchymal responses via mitogen-activated protein kinase kinase, p38, and nuclear factor kappaB in human endometriotic epithelial cells. Mol. Pharmacol. 73:1394–1404, 2008.CrossRefGoogle Scholar
  25. 25.
    Gu, X., and K. S. Masters. Regulation of valvular interstitial cell calcification by adhesive peptide sequences. J. Biomed. Mater. Res. A 93:1620–1630, 2010.Google Scholar
  26. 26.
    Harrington, D. J., B. A. Lessey, V. Rai, A. Bergqvist, S. Kennedy, S. Manek, D. H. Barlow, and H. J. Mardon. Tenascin is differentially expressed in endometrium and endometriosis. J. Pathol. 187:242–248, 1999.CrossRefGoogle Scholar
  27. 27.
    Hayman, E. G., M. D. Pierschbacher, S. Suzuki, and E. Ruoslahti. Vitronectin—a major cell attachment-promoting protein in fetal bovine serum. Exp. Cell Res. 160:245–258, 1985.CrossRefGoogle Scholar
  28. 28.
    Hong, H., and J. P. Stegemann. 2D and 3D collagen and fibrin biopolymers promote specific ECM and integrin gene expression by vascular smooth muscle cells. J. Biomater. Sci. Polym. Ed. 19:1279–1293, 2008.CrossRefGoogle Scholar
  29. 29.
    Johnson, P. J., A. Tatara, D. A. McCreedy, A. Shiu, and S. E. Sakiyama-Elbert. Tissue-engineered fibrin scaffolds containing neural progenitors enhance functional recovery in a subacute model of SCI. Soft Matter 6:5127–5137, 2010.CrossRefGoogle Scholar
  30. 30.
    Kim, J. H., and A. R. Asthagiri. Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation. J. Cell Sci. 124:1280–1287, 2011.CrossRefGoogle Scholar
  31. 31.
    Klemmt, P. A., J. G. Carver, P. Koninckx, E. J. McVeigh, and H. J. Mardon. Endometrial cells from women with endometriosis have increased adhesion and proliferative capacity in response to extracellular matrix components: towards a mechanistic model for endometriosis progression. Hum. Reprod. 22:3139–3147, 2007.CrossRefGoogle Scholar
  32. 32.
    Kondera-Anasz, Z., J. Sikora, A. Mielczarek-Palacz, and M. Jonca. Concentrations of interleukin (IL)-1alpha, IL-1 soluble receptor type II (IL-1 sRII) and IL-1 receptor antagonist (IL-1 Ra) in the peritoneal fluid and serum of infertile women with endometriosis. Eur. J. Obstet. Gynecol. Reprod. Biol. 123:198–203, 2005.CrossRefGoogle Scholar
  33. 33.
    Kreeger, P. K., J. W. Deck, T. K. Woodruff, and L. D. Shea. The in vitro regulation of ovarian follicle development using alginate-extracellular matrix gels. Biomaterials 27:714–723, 2006.CrossRefGoogle Scholar
  34. 34.
    Kyama, C. M., S. Debrock, J. M. Mwenda, and T. M. D’Hooghe. Potential involvement of the immune system in the development of endometriosis. Reprod. Biol. Endocrinol. 1:123, 2003.CrossRefGoogle Scholar
  35. 35.
    Leach, R. E., R. Khalifa, N. D. Ramirez, S. K. Das, J. Wang, S. K. Dey, R. Romero, and D. R. Armant. Multiple roles for heparin-binding epidermal growth factor-like growth factor are suggested by its cell-specific expression during the human endometrial cycle and early placentation. J. Clin. Endocrinol. Metab. 84:3355–3363, 1999.Google Scholar
  36. 36.
    Lebovic, D. I., M. D. Mueller, and R. N. Taylor. Immunobiology of endometriosis. Fertil. Steril. 75:1–10, 2001.CrossRefGoogle Scholar
  37. 37.
    Lee, G. Y., P. A. Kenny, E. H. Lee, and M. J. Bissell. Three-dimensional culture models of normal and malignant breast epithelial cells. Nat. Methods 4:359–365, 2007.CrossRefGoogle Scholar
  38. 38.
    Li, M. L., J. Aggeler, D. A. Farson, C. Hatier, J. Hassell, and M. J. Bissell. Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells. Proc. Natl. Acad. Sci. USA 84:136–140, 1987.CrossRefGoogle Scholar
  39. 39.
    Li, D., J. Chen, Z. Gao, X. Li, X. Yan, Y. Xiong, and S. Wang. 67-kDa laminin receptor in human bile duct carcinoma. Eur. Surg. Res. 42:168–173, 2009.CrossRefGoogle Scholar
  40. 40.
    Li, M. Q., X. Z. Luo, Y. H. Meng, J. Mei, X. Y. Zhu, L. P. Jin, and D. J. Li. CXCL8 enhances proliferation and growth and reduces apoptosis in endometrial stromal cells in an autocrine manner via a CXCR1-triggered PTEN/AKT signal pathway. Hum. Reprod. 27:2107–2116, 2012.CrossRefGoogle Scholar
  41. 41.
    Lin, W., S. Chen, M. Li, B. Wang, X. Qu, and Y. Zhang. Expression of macrophage migration inhibitory factor in human endometriosis: relation to disease stage, menstrual cycle and infertility. J. Obstet. Gynaecol. Res. 36:344–351, 2010.CrossRefGoogle Scholar
  42. 42.
    Loh, F. H., A. Bongso, C. Y. Fong, D. R. Koh, S. H. Lee, and H. Q. Zhao. Effects of peritoneal macrophages from women with endometriosis on endometrial cellular proliferation in an in vitro coculture model. Fertil. Steril. 72:533–538, 1999.CrossRefGoogle Scholar
  43. 43.
    Lowell, C. A., and T. N. Mayadas. Overview: studying integrins in vivo. Methods Mol. Biol. 757:369–397, 2012.CrossRefGoogle Scholar
  44. 44.
    Malhotra, N., D. Karmakar, V. Tripathi, K. Luthra, and S. Kumar. Correlation of angiogenic cytokines-leptin and IL-8 in stage, type and presentation of endometriosis. Gynecol. Endocrinol. 28(3):224–227, 2012.CrossRefGoogle Scholar
  45. 45.
    Matsuzaki, S., and C. Darcha. Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis. Hum. Reprod. 27:712–721, 2012.CrossRefGoogle Scholar
  46. 46.
    Miller, M. A., A. S. Meyer, M. T. Beste, Z. Lasisi, S. Reddy, K. W. Jeng, C. H. Chen, J. Han, K. Isaacson, L. G. Griffith, and D. A. Lauffenburger. ADAM-10 and -17 regulate endometriotic cell migration via concerted ligand and receptor shedding feedback on kinase signaling. Proc. Natl. Acad. Sci. USA 110:E2074–E2083, 2013.CrossRefGoogle Scholar
  47. 47.
    Muranen, T., L. M. Selfors, D. T. Worster, M. P. Iwanicki, L. Song, F. C. Morales, S. Gao, G. B. Mills, and J. S. Brugge. Inhibition of PI3 K/mTOR leads to adaptive resistance in matrix-attached cancer cells. Cancer Cell 21:227–239, 2012.CrossRefGoogle Scholar
  48. 48.
    Peyton, S. R., C. M. Ghajar, C. B. Khatiwala, and A. J. Putnam. The emergence of ECM mechanics and cytoskeletal tension as important regulators of cell function. Cell Biochem. Biophys. 47:300–320, 2007.CrossRefGoogle Scholar
  49. 49.
    Provenzano, P. P., K. W. Eliceiri, J. M. Campbell, D. R. Inman, J. G. White, and P. J. Keely. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med. 4:38, 2006.CrossRefGoogle Scholar
  50. 50.
    Raub, C. B., A. J. Putnam, B. J. Tromberg, and S. C. George. Predicting bulk mechanical properties of cellularized collagen gels using multiphoton microscopy. Acta Biomater. 6:4657–4665, 2010.CrossRefGoogle Scholar
  51. 51.
    Rodriguez, K. J., and K. S. Masters. Regulation of valvular interstitial cell calcification by components of the extracellular matrix. J. Biomed. Mater. Res. A 90:1043–1053, 2009.CrossRefGoogle Scholar
  52. 52.
    Scholl, B., N. A. Bersinger, A. Kuhn, and M. D. Mueller. Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis. Gynecol. Endocrinol. 25:701–706, 2009.CrossRefGoogle Scholar
  53. 53.
    Song, T., C. H. Choi, Y. J. Cho, C. O. Sung, S. Y. Song, T. J. Kim, D. S. Bae, J. W. Lee, and B. G. Kim. Expression of 67-kDa laminin receptor was associated with tumor progression and poor prognosis in epithelial ovarian cancer. Gynecol. Oncol. 125:427–432, 2012.CrossRefGoogle Scholar
  54. 54.
    Soofi, S. S., J. A. Last, S. J. Liliensiek, P. F. Nealey, and C. J. Murphy. The elastic modulus of Matrigel as determined by atomic force microscopy. J. Struct. Biol. 167:216–219, 2009.CrossRefGoogle Scholar
  55. 55.
    Thiery, J. P. Epithelial–mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2:442–454, 2002.CrossRefGoogle Scholar
  56. 56.
    Tsuchiya, S., Y. Kobayashi, Y. Goto, H. Okumura, S. Nakae, T. Konno, and K. Tada. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 42:1530–1536, 1982.Google Scholar
  57. 57.
    Vercellini, P., P. Vigano, E. Somigliana, and L. Fedele. Endometriosis: pathogenesis and treatment. Nat. Rev. Endocrinol. 10:261–275, 2014.Google Scholar
  58. 58.
    Waugh, D. J., and C. Wilson. The interleukin-8 pathway in cancer. Clin. Cancer Res. 14:6735–6741, 2008.CrossRefGoogle Scholar
  59. 59.
    Weaver, V. M., A. H. Fischer, O. W. Peterson, and M. J. Bissell. The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay. Biochem. Cell Biol. 74:833–851, 1996.CrossRefGoogle Scholar
  60. 60.
    Wu, M. Y., and H. N. Ho. The role of cytokines in endometriosis. Am. J. Reprod. Immunol. 49:285–296, 2003.CrossRefGoogle Scholar
  61. 61.
    Wu, Y., A. Starzinski-Powitz, and S. W. Guo. Constitutive and tumor necrosis factor-alpha-stimulated activation of nuclear factor-kappaB in immortalized endometriotic cells and their suppression by trichostatin A. Gynecol. Obstet. Investig. 70:23–33, 2010.CrossRefGoogle Scholar
  62. 62.
    Yang, J., J. Richards, P. Bowman, R. Guzman, J. Enami, K. McCormick, S. Hamamoto, D. Pitelka, and S. Nandi. Sustained growth and three-dimensional organization of primary mammary tumor epithelial cells embedded in collagen gels. Proc. Natl. Acad. Sci. USA 76:3401–3405, 1979.CrossRefGoogle Scholar
  63. 63.
    Yoo, H. J., D. H. Barlow, and H. J. Mardon. Temporal and spatial regulation of expression of heparin-binding epidermal growth factor-like growth factor in the human endometrium: a possible role in blastocyst implantation. Dev. Genet. 21:102–108, 1997.CrossRefGoogle Scholar
  64. 64.
    Zeitvogel, A., R. Baumann, and A. Starzinski-Powitz. Identification of an invasive, N-cadherin-expressing epithelial cell type in endometriosis using a new cell culture model. Am. J. Pathol. 159:1839–1852, 2001.CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  • Kathryn Pollock
    • 1
  • Taylor J. Jaraczewski
    • 1
  • Molly J. Carroll
    • 1
  • Dan I. Lebovic
    • 2
  • Pamela K. Kreeger
    • 1
  1. 1.Department of Biomedical EngineeringUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of Obstetrics and GynecologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA

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