Relaxins enhance growth of spontaneous murine breast cancers as well as metastatic colonization of the brain

Clinical and Experimental Metastasis

Volumn 31, Issue 1, 2014, Pages 57-65

  Binder, Claudia ^a   Chuang, Eugenia ^a   Habla, Christina ^b   Bleckmann, Annalen ^a   Schulz, Matthias ^a   Bathgate, Ross ^c   Einspanier, Almuth ^b  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

^b UNIVERSITY OF LEIPZIG   (Germany)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Brain metastasis; Breast cancer; Relaxin; RXFP1; Tg(MMTV erbB2) mouse model

Indexed keywords

EID: 84895046060     PISSN: 02620898     EISSN: 15737276     Source Type: Journal    
DOI: 10.1007/s10585-013-9609-2     Document Type: Article

References (38)

1. Samuel CS, Lekgabe ED, Mookerjee I (2007) The effects of relaxin on extracellular matrix remodeling in health and fibrotic disease. Adv Exp Med Biol 612:88-103
2. Segal MS, Sautina L, Li S, Diao Y, Agoulnik AI, Kielczewski J, McGuane JT, Grant MB, Conrad KP (2011) Relaxin increases human endothelial progenitor cell NO and migration and vasculogenesis in mice. Blood 119:326-327
3. Silvertown JD, Ng J, Sato T, Summerlee AJ, Medin JA (2006) H2 relaxin overexpression increases in vivo prostate xenograft tumor growth and angiogenesis. Int J Cancer 118:62-73
4. Silvertown JD, Symes JC, Neschadim A, Nonaka T, Kao JC, Summerlee AJ, Medin JA (2007) Analog of H2 relaxin exhibits antagonistic properties and impairs prostate tumor growth. FASEB J 21:754-765
5. Feng S, Agoulnik IU, Truong A, Li Z, Creighton CJ, Kaftanovskaya EM, Pereira R, Han HD, Lopez-Berestein G, Klonisch T, Ittmann MM, Sood AK, Agoulnik AI (2010) Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis. Endocr Relat Cancer 17:1021-1033
6. Thompson VC, Morris TG, Cochrane DR, Cavanagh J, Wafa LA, Hamilton T, Wang S, Fazli L, Gleave ME, Nelson CC (2006) Relaxin becomes upregulated during prostate cancer progression to androgen independence and is negatively regulated by androgens. Prostate 66:1698-1709
7. Feng S, Agoulnik IU, Bogatcheva NV, Kamat AA, Kwabi-Addo B, Li R, Ayala G, Ittmann MM, Agoulnik AI (2007) Relaxin promotes prostate cancer progression. Clin Cancer Res 13:1695-1702
8. Bialek J, Kunanuvat U, Hombach-Klonisch S, Spens A, Stetefeld J, Sunley K, Lippert D, Wilkins JA, Hoang-Vu C, Klonisch T (2011) Relaxin enhances the collagenolytic activity and in vitro invasiveness by upregulating matrix metalloproteinases in human thyroid carcinoma cells. Mol Cancer Res 9:673-687
9. Radestock Y, Willing C, Kehlen A, Hoang-Vu C, Hombach-Klonisch S (2010) Relaxin enhances S100A4 and promotes growth of human thyroid carcinoma cell xenografts. Mol Cancer Res 8:494-506
10. Kamat AA, Feng S, Agoulnik IU, Kheradmand F, Bogatcheva NV, Coffey D, Sood AK, Agoulnik AI (2006) The role of relaxin in endometrial cancer. Cancer Biol Ther 5:71-77
11. Tashima LS, Mazoujian G, Bryant-Greenwood GD (1994) Human relaxins in normal, benign and neoplastic breast tissue. J Mol Endocrinol 12:351-364
12. Bani D, Flagiello D, Poupon MF, Nistri S, Poirson-Bichat F, Bigazzi M, Bani ST (1999) Relaxin promotes differentiation of human breast cancer cells MCF-7 transplanted into nude mice. Virchows Arch 435:509-519
13. Radestock Y, Hoang-Vu C, Hombach-Klonisch S (2008) Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells. Breast Cancer Res 10:R71
14. Sacchi TB, Bani D, Brandi ML, Falchetti A, Bigazzi M (1994) Relaxin influences growth, differentiation and cell-cell adhesion of human breast-cancer cells in culture. Int J Cancer 57:129-134
15. Binder C, Hagemann T, Husen B, Schulz M, Einspanier A (2002) Relaxin enhances in vitro invasiveness of breast cancer cell lines by up-regulation of matrix metalloproteases. Mol Hum Reprod 8:789-796
16. Hossain MA, Samuel CS, Binder C, Hewitson TD, Tregear GW, Wade JD, Bathgate RA (2010) The chemically synthesized human relaxin-2 analog, B-R13/17 K H2, is an RXFP1 antagonist. Amino Acids 39:409-416
17. Binder C, Simon A, Binder L, Hagemann T, Schulz M, Emons G, Trumper L, Einspanier A (2004) Elevated concentrations of serum relaxin are associated with metastatic disease in breast cancer patients. Breast Cancer Res Treat 87:157-166
18. Sica A, Schioppa T, Mantovani A, Allavena P (2006) Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur JCancer 42:717-727
19. Pukrop T, Dehghani F, Chuang HN, Lohaus R, Bayanga K, Heermann S, Regen T, Van Rossum D, Klemm F, Schulz M, Siam L, Hoffmann A, Trumper L, Stadelmann C, Bechmann I, Hanisch UK, Binder C (2010) Microglia promote colonization of brain tissue by breast cancer cells in a Wnt-dependent way. Glia 58:1477-1489
20. Pukrop T, Klemm F, Hagemann T, Gradl D, Schulz M, Siemes S, Trumper L, Binder C (2006) Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc Natl Acad Sci USA 103:5454-5459
21. Figueiredo KA, Rossi G, Cox ME (2009) Relaxin promotes clustering, migration, and activation states of mononuclear myelocytic cells. Ann N Y Acad Sci 1160:353-360
22. Boggio K, Nicoletti G, Di CE, Cavallo F, Landuzzi L, Melani C, Giovarelli M, Rossi I, Nanni P, De GC, Bouchard P, Wolf S, Modesti A, Musiani P, Lollini PL, Colombo MP, Forni G (1998) Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice. J Exp Med 188:589-596
23. Olson EM, Abdel-Rasoul M, Maly J, Wu CS, Lin NU, Shapiro CL (2013) Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab. Ann Oncol. doi: 10.1093/annonc/mdt036
24. Einspanier A, Nubbemeyer R, Schlote S, Schumacher M, Ivell R, Fuhrmann K, Marten A (1999) Relaxin in the marmoset monkey: secretion pattern in the ovarian cycle and early pregnancy. Biol Reprod 61:512-520
25. Ivell R, Balvers M, Pohnke Y, Telgmann R, Bartsch O, Milde-Langosch K, Bamberger AM, Einspanier A (2003) Immunoexpression of the relaxin receptor LGR7 in breast and uterine tissues of humans and primates. Reprod Biol Endocrinol 1:114-127
26. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156-159
27. Heng K, Ivell R, Wagaarachchi P, Anand-Ivell R (2008) Relaxin signalling in primary cultures of human myometrial cells. Mol Hum Reprod 14:603-611
28. Smith CM, Shen PJ, Banerjee A, Bonaventure P, Ma S, Bathgate RA, Sutton SW, Gundlach AL (2010) Distribution of relaxin-3 and RXFP3 within arousal, stress, affective, and cognitive circuits of mouse brain. J Comp Neurol 518:4016-4045
29. Kong RC, Shilling PJ, Lobb DK, Gooley PR, Bathgate RA (2010) Membrane receptors: structure and function of the relaxin family peptide receptors. Mol Cell Endocrinol 320:1-15
30. Simon C, Einspanier A (2009) The hormonal induction of cervical remodeling in the common marmoset monkey (Callithrix jacchus). Reproduction 137:517-525
31. Yan W, Chen J, Wiley AA, Crean-Harris BD, Bartol FF, Bagnell CA (2008) Relaxin (RLX) and estrogen affect estrogen receptor alpha, vascular endothelial growth factor, and RLX receptor expression in the neonatal porcine uterus and cervix. Reproduction 135:705-712
32. Yao L, Cooke PS, Meling DD, Shanks RD, Jameson JL, Sherwood OD (2010) The effect of relaxin on cell proliferation in mouse cervix requires estrogen receptor alpha binding to estrogen response elements in stromal cells. Endocrinology 151:2811-2818
33. Leek RD, Harris AL (2002) Tumor-associated macrophages in breast cancer. J Mammary Gland Biol Neoplasia 7:177-189
34. Lamp O, Honscha KU, Schweizer S, Heckmann A, Blaschzik S, Einspanier A (2013) The metastatic potential of canine mammary tumours can be assessed by mRNA expression analysis of connective tissue modulators. Vet Comp Oncol 11:70-85
35. Beyer I, Li Z, Persson J, Liu Y, Van Rensburg R, Yumul R, Zhang XB, Hung MC, Lieber A (2011) Controlled extracellular matrix degradation in breast cancer tumors improves therapy by trastuzumab. Mol Ther 19:479-489
36. Li Z, Liu Y, Tuve S, Xun Y, Fan X, Min L, Feng Q, Kiviat N, Kiem HP, Disis ML, Lieber A (2009) Toward a stem cell gene therapy for breast cancer. Blood 113:5423-5433
37. Piccinni MP, Bani D, Beloni L, Manuelli C, Mavilia C, Vocioni F, Bigazzi M, Sacchi TB, Romagnani S, Maggi E (1999) Relaxin favors the development of activated human T cells into Th1-like effectors. Eur J Immunol 29:2241-2247
38. Pukrop T, Bleckmann A, Einspanier A, Binder C (2009) Rapid progression of hormone receptor-negative breast cancer concomitant with ovarian stimulation - a paradoxon? Ann Oncol 20:2020-2022