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Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model

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Abstract

Fatal outcomes of prostate carcinoma (PCa) mostly result from metastatic spread rather than from primary tumor burden. Here, we monitored growth and metastatic spread of an orthotopic luciferase/GFP-expressing LNCaP PCa xenograft model in SCID mice by in vivo imaging and in vitro luciferase assay of tissues homogenates. Although the metastatic spread generally shows a significant correlation to primary tumor volumes, the susceptibility of various tissues to metastatic invasion was different in the number of affected animals as well as in absolute metastatic burden in the individual tissues. Using this xenograft model we showed that treatment with liposomal gemcitabine (GemLip) inhibited growth of the primary tumors (83.9 ± 6.4%; P = 0.009) as well as metastatic burden in lymph nodes (95.6 ± 24.0%; P = 0.047), lung (86.5 ± 10.5%; P = 0.015), kidney (88.4 ± 9.2%; P = 0.045) and stomach (79.5 ± 6.6%; P = 0.036) already at very low efficient concentrations (8 mg/kg) as compared to conventional gemcitabine (360 mg/kg). Our data show that this orthotopic LNCaP xenograft PCa model seems to reflect the clinical situation characterized by the fact that at time of diagnosis, prostate neoplasms are biologically heterogeneous and thus, it is a useful model to investigate new anti-metastatic therapies.

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Abbreviations

PCa:

Prostate carcinoma

GemLip:

Liposomal gemcitabine

Gemc:

Gemcitabine

SCID:

Severe combined immunodeficiency disease

dFdC:

2′,2′-Difluoro-2′-deoxycytidine

RLU:

Relative light units

ph/s:

Photons per second

MTD:

Maximal tolerable dose

EPR:

Enhanced permeability and retention effect

GFP:

Green fluorescent protein

References

  1. Greenlee RT, Hill-Harmon MB, Murray T et al (2001) Cancer statistics, 2001. CA Cancer J Clin 51:15–36

    Article  PubMed  CAS  Google Scholar 

  2. Jemal A, Thomas A, Murray T et al (2002) Cancer statistics, 2002. CA Cancer J Clin 52:23–47

    Article  PubMed  Google Scholar 

  3. Bertz J, Giersiepen K, Haberland J et al (eds) (2006) Krebs in Deutschland. Häufigkeiten und Trends, 5th edn. Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (GEKID) & Robert Koch-Institut (RKI), Saarbrücken

  4. Vantyghem SA, Wilson SM, Postenka CO et al (2005) Dietary genistein reduces metastasis in a postsurgical orthotopic breast cancer model. Cancer Res 65:3396–3403

    PubMed  CAS  Google Scholar 

  5. Weckermann D, Goppelt M, Dorn R et al (2006) Incidence of positive pelvic lymph nodes in patients with prostate cancer, a prostate-specific antigen (PSA) level of ≤ 10 ng/mL and biopsy Gleason score of ≤ 6, and their influence on PSA progression-free survival after radical prostatectomy. BJU Int 97:1173–1178

    Article  PubMed  Google Scholar 

  6. de Wit R (2008) Chemotherapy in hormone-refractory prostate cancer. BJU Int 101(Suppl 2):11–15

    Article  PubMed  Google Scholar 

  7. Nelson JB, Hedican SP, George DJ et al (1995) Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1:944–949

    Article  PubMed  CAS  Google Scholar 

  8. Wang Y, Xue H, Cutz JC et al (2005) An orthotopic metastatic prostate cancer model in SCID mice via grafting of a transplantable human prostate tumor line. Lab Invest 85:1392–1404

    Article  PubMed  Google Scholar 

  9. Lam JS, Yamashiro J, Shintaku IP et al (2005) Prostate stem cell antigen is overexpressed in prostate cancer metastases. Clin Cancer Res 11:2591–2596

    Article  PubMed  CAS  Google Scholar 

  10. Msaouel P, Pissimissis N, Halapas A et al (2008) Mechanisms of bone metastasis in prostate cancer: clinical implications. Best Pract Res Clin Endocrinol Metab 22:341–355

    Article  PubMed  CAS  Google Scholar 

  11. Sweeney P, Karashima T, Kim SJ et al (2002) Anti-vascular endothelial growth factor receptor 2 antibody reduces tumorigenicity and metastasis in orthotopic prostate cancer xenografts via induction of endothelial cell apoptosis and reduction of endothelial cell matrix metalloproteinase type 9 production. Clin Cancer Res 8:2714–2724

    PubMed  CAS  Google Scholar 

  12. Wu TT, Sikes RA, Cui Q et al (1998) Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. Int J Cancer 77:887–894

    Article  PubMed  CAS  Google Scholar 

  13. Dumont P, Petein M, Lespagnard L et al (1993) Unusual behaviour of the LNCaP prostate tumour xenografted in nude mice. In Vivo 7:167–170

    PubMed  CAS  Google Scholar 

  14. Yonou H, Kanomata N, Goya M et al (2003) Osteoprotegerin/osteoclastogenesis inhibitory factor decreases human prostate cancer burden in human adult bone implanted into nonobese diabetic/severe combined immunodeficient mice. Cancer Res 63:2096–2102

    PubMed  CAS  Google Scholar 

  15. Rembrink K, Romijn JC, van der Kwast TH et al (1997) Orthotopic implantation of human prostate cancer cell lines: a clinically relevant animal model for metastatic prostate cancer. Prostate 31:168–174

    Article  PubMed  CAS  Google Scholar 

  16. Langley RR, Fidler IJ (2007) Tumor cell-organ microenvironment interactions in the pathogenesis of cancer metastasis. Endocr Rev 28:297–321

    Article  PubMed  CAS  Google Scholar 

  17. Talmadge JE, Singh RK, Fidler IJ et al (2007) Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol 170:793–804

    Article  PubMed  CAS  Google Scholar 

  18. Havens AM, Pedersen EA, Shiozawa Y et al (2008) An in vivo mouse model for human prostate cancer metastasis. Neoplasia 10:371–380

    PubMed  CAS  Google Scholar 

  19. Stephenson RA, Dinney CP, Gohji K et al (1992) Metastatic model for human prostate cancer using orthotopic implantation in nude mice. JNCI 84:951–957

    Article  PubMed  CAS  Google Scholar 

  20. Graeser R, Chung DE, Esser N et al (2008) Synthesis and biological evaluation of an albumin-binding prodrug of doxorubicin that is cleaved by prostate-specific antigen (PSA) in a PSA-positive orthotopic prostate carcinoma model (LNCaP). Int J Cancer 122:1145–1154

    Article  PubMed  CAS  Google Scholar 

  21. Busby JE, Kim SJ, Yazici S et al (2006) Therapy of multidrug resistant human prostate tumors in the prostate of nude mice by simultaneous targeting of the epidermal growth factor receptor and vascular endothelial growth factor receptor on tumor-associated endothelial cells. Prostate 66:1788–1798

    Article  PubMed  CAS  Google Scholar 

  22. Cassinelli G, Lanzi C, Supino R et al (2002) Cellular bases of the antitumor activity of the novel taxane IDN 5109 (BAY59–8862) on hormone-refractory prostate cancer. Clin Cancer Res 8:2647–2654

    PubMed  CAS  Google Scholar 

  23. Bergman AM, Pinedo HM, Talianidis I et al (2003) Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines. Br J Cancer 88:1963–1970

    Article  PubMed  CAS  Google Scholar 

  24. Cronauer MV, Klocker H, Talasz H et al (1996) Inhibitory effects of the nucleoside analogue gemcitabine on prostatic carcinoma cells. Prostate 28:172–181

    Article  PubMed  CAS  Google Scholar 

  25. Muenchen HJ, Quigley MM, Pilat MJ et al (2000) The study of gemcitabine in combination with other chemotherapeutic agents as an effective treatment for prostate cancer. Anticancer Res 20:735–740

    PubMed  CAS  Google Scholar 

  26. Zhang C, Mattern J, Haferkamp A et al (2006) Corticosteroid-induced chemotherapy resistance in urological cancers. Cancer Biol Ther 5:59–64

    Article  PubMed  CAS  Google Scholar 

  27. Vogelzang NJ (2002) Future directions for gemcitabine in the treatment of genitourinary cancer. Semin Oncol 29:40–45

    Article  PubMed  Google Scholar 

  28. Pagliaro LC, Delpassand ES, Williams D et al (2003) A phase I/II study of strontium-89 combined with gemcitabine in the treatment of patients with androgen independent prostate carcinoma and bone metastases. Cancer 97:2988–2994

    Article  PubMed  CAS  Google Scholar 

  29. Rodney A, Dieringer P, Mathew P et al (2006) Phase II study of capecitabine combined with gemcitabine in the treatment of androgen-independent prostate cancer previously treated with taxanes. Cancer 106:2143–2147

    Article  PubMed  CAS  Google Scholar 

  30. Moog R, Burger AM, Brandl M et al (2002) Change in pharmacokinetic and pharmacodynamic behavior of gemcitabine in human tumor xenografts upon entrapment in vesicular phospholipid gels. Cancer Chemother Pharmacol 49:356–366

    Article  PubMed  CAS  Google Scholar 

  31. Bornmann C, Graeser R, Esser N et al (2008) A new liposomal formulation of gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging. Cancer Chemother Pharmacol 61:395–405

    Article  PubMed  CAS  Google Scholar 

  32. Graeser R, Bornmann C, Esser N et al (2009) Antimetastatic effects of liposomal gemcitabine and empty liposomes in an orthotopic mouse model of pancreatic cancer. Pancreas 38:330–337

    Article  PubMed  CAS  Google Scholar 

  33. Scatena CD, Hepner MA, Oei YA et al (2004) Imaging of bioluminescent LNCaP-luc-M6 tumors: a new animal model for the study of metastatic human prostate cancer. Prostate 59:292–303

    Article  PubMed  CAS  Google Scholar 

  34. Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 89:5547–5551

    Article  PubMed  CAS  Google Scholar 

  35. Tardi C (1999) Vesikuläre Phospholipidgele: in vitro Charakterisierung, Autoklavierbarkeit, Anwendung als Depotarzneiform. PhD Thesis, Department of Pharmaceutical Technology, University of Freiburg, Germany

  36. Brandl M, Massing U (2003) Vesicular phospholipid gels. In: Weissig V, Torchillin V (eds) Liposomes: a practical approach, vol 170. Oxford University Press, Oxford

    Google Scholar 

  37. Workman P, Balmain A, Hickman JA et al (1988) UKCCCR guidelines for the welfare of animals in experimental neoplasia. Lab Anim 22:195–201

    Article  PubMed  CAS  Google Scholar 

  38. Fastaia J, Dumont AE (1976) Pathogenesis of ascites in mice with peritoneal carcinomatosis. J Natl Cancer Inst 56:547–550

    PubMed  CAS  Google Scholar 

  39. Roberts WG, Hasan T (1992) Role of neovasculature and vascular permeability on the tumor retention of photodynamic agents. Cancer Res 52:924–930

    PubMed  CAS  Google Scholar 

  40. Kasman L, Lu P, Voelkel-Johnson C (2007) The histone deacetylase inhibitors depsipeptide and MS-275, enhance TRAIL gene therapy of LNCaP prostate cancer cells without adverse effects in normal prostate epithelial cells. Cancer Gene Ther 14:327–334

    Article  PubMed  CAS  Google Scholar 

  41. Zisman A, Ng CP, Pantuck AJ et al (2001) Actinomycin D and gemcitabine synergistically sensitize androgen-independent prostate cancer cells to Apo2L/TRAIL-mediated apoptosis. J Immunother 24:459–471

    Article  PubMed  CAS  Google Scholar 

  42. Maeda H, Segawa T, Kamoto T et al (2000) Rapid detection of candidate metastatic foci in the orthotopic inoculation model of androgen-sensitive prostate cancer cells introduced with green fluorescent protein. Prostate 45:335–340

    Article  PubMed  CAS  Google Scholar 

  43. Hoffman R (2002) Green fluorescent protein imaging of tumour growth, metastasis, and angiogenesis in mouse models. Lancet Oncol 3:546–556

    Article  PubMed  CAS  Google Scholar 

  44. Glinskii AB, Smith BA, Jiang P et al (2003) Viable circulating metastatic cells produced in orthotopic but not ectopic prostate cancer models. Cancer Res 63:4239–4243

    PubMed  CAS  Google Scholar 

  45. Tuxhorn JA, McAlhany SJ, Dang TD et al (2002) Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model. Cancer Res 62:3298–3307

    PubMed  CAS  Google Scholar 

  46. Downing S, Bumak C, Nixdorf S et al (2003) Elevated levels of prostate-specific antigen (PSA) in prostate cancer cells expressing mutant p53 is associated with tumor metastasis. Mol Carcinog 38:130–140

    Article  PubMed  CAS  Google Scholar 

  47. Wu GJ, Peng Q, Fu P et al (2004) Ectopical expression of human MUC18 increases metastasis of human prostate cancer cells. Gene 327:201–213

    Article  PubMed  CAS  Google Scholar 

  48. Jantscheff P, Reisen J, Sticker M et al (2005) GPI-linked CEACAM6 molecule expression in prostate cancer (abstract). Onkologie 28:50

    Google Scholar 

  49. Jantscheff P, Terracciano L, Lowy A et al (2003) Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance. J Clin Oncol 21:3638–3646

    Article  PubMed  CAS  Google Scholar 

  50. Duxbury MS, Ito H, Benoit E et al (2004) Overexpression of CEACAM6 promotes insulin-like growth factor I-induced pancreatic adenocarcinoma cellular invasiveness. Oncogene 23:5834

    Article  PubMed  CAS  Google Scholar 

  51. Blumenthal RD, Hansen HJ, Goldenberg DM (2005) Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen). Cancer Res 65:8809–8817

    Article  PubMed  CAS  Google Scholar 

  52. Ariztia EV, Lee CJ, Gogoi R et al (2006) The tumor microenvironment: key to early detection. Crit Rev Clin Lab Sci 43:393–425

    Article  PubMed  CAS  Google Scholar 

  53. Mirchandani D, Zheng J, Miller GJ et al (1995) Heterogeneity in intratumor distribution of p53 mutations in human prostate cancer. Am J Pathol 147:92–101

    PubMed  CAS  Google Scholar 

  54. Konishi N, Hiasa Y, Matsuda H et al (1995) Intratumor cellular heterogeneity and alterations in ras oncogene and p53 tumor suppressor gene in human prostate carcinoma. Am J Pathol 147:1112–1122

    PubMed  CAS  Google Scholar 

  55. Navone NM, Olive M, Ozen M et al (1997) Establishment of two human prostate cancer cell lines derived from a single bone metastasis. Clin Cancer Res 3:2493–2500

    PubMed  CAS  Google Scholar 

  56. Olapade-Olaopa EO, MacKay EH, Taub NA et al (1999) Malignant transformation of human prostatic epithelium is associated with the loss of androgen receptor immunoreactivity in the surrounding stroma. Clin Cancer Res 5:569–576

    PubMed  CAS  Google Scholar 

  57. Fidler IJ, Kim SJ, Langley RR (2007) The role of the organ microenvironment in the biology and therapy of cancer metastasis. J Cell Biochem 101:927–936

    Article  PubMed  CAS  Google Scholar 

  58. Thalmann GN, Anezinis PE, Chang SM et al (1994) Androgen-independent cancer progression and bone metastasis in the LNCaP model of human prostate cancer. Cancer Res 54:2577–2581

    PubMed  CAS  Google Scholar 

  59. McConkey DJ, Greene G, Pettaway CA (1996) Apoptosis resistance increases with metastatic potential in cells of the human LNCaP prostate carcinoma line. Cancer Res 56:5594–5599

    PubMed  CAS  Google Scholar 

  60. Rhee HW, Zhau HE, Pathak S et al (2001) Permanent phenotypic and genotypic changes of prostate cancer cells cultured in a three-dimensional rotating-wall vessel. In Vitro Cell Dev Biol Anim 37:127–140

    Article  PubMed  CAS  Google Scholar 

  61. Freedland SJ, Pantuck AJ, Paik SH et al (2003) Heterogeneity of molecular targets on clonal cancer lines derived from a novel hormone-refractory prostate cancer tumor system. Prostate 55:299–307

    Article  PubMed  CAS  Google Scholar 

  62. Richards DA (2005) Chemotherapeutic gemcitabine doublets in pancreatic carcinoma. Semin Oncol 32:S9–S13

    Article  PubMed  CAS  Google Scholar 

  63. Boulikas T, Vougiouka M (2004) Recent clinical trials using cisplatin, carboplatin and their combination chemotherapy drugs (review). Oncol Rep 11:559–595

    PubMed  CAS  Google Scholar 

  64. Gabizon AA, Shmeeda H, Zalipsky S (2006) Pros and cons of the liposome platform in cancer drug targeting. J Liposome Res 16:175–183

    Article  PubMed  CAS  Google Scholar 

  65. Yuan F, Dellian M, Fukumura D et al (1995) Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res 55:3752–3756

    PubMed  CAS  Google Scholar 

  66. Massing U (1997) Cancer therapy with liposomal formulations of anticancer drugs. Int J Clin Pharmacol Ther 35:87–90

    PubMed  CAS  Google Scholar 

  67. Ludemann L, Grieger W, Wurm R et al (2005) Quantitative measurement of leakage volume and permeability in gliomas, meningiomas and brain metastases with dynamic contrast-enhanced MRI. Magn Reson Imaging 23:833–841

    Article  PubMed  Google Scholar 

  68. Jantscheff P, Esser N, Graeser R et al (2009) Liposomal gemcitabine (GemLip)-efficient drug against hormone-refractory Du145 and PC-3 prostate cancer xenografts. Prostate 69:1151–1163

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Dietmar Hopp Stiftung GmbH and the Kirstins Weg, Stiftung e.V.

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Author notes

  1. Alena Sukolinskaya

    Present address: N.N. Alexandrov National Cancer Center of Belarus, Minsk, Belarus

Authors and Affiliations

  1. Department of Clinical Research, Tumor Biology Center, Freiburg, Germany

    Peter Jantscheff, Vittorio Ziroli, Jessica Kluth, Alena Sukolinskaya, Lenka A. Taylor & Ulrich Massing

  2. ProQinase GmbH, Freiburg, Germany

    Norbert Esser & Ralph Graeser

  3. Clinic of Medical Oncology & Department of Clinical Research, Tumor Biology Center, Freiburg, Germany

    Clemens Unger

  4. Clinical Research, Department of Lipids & Liposomes, Tumor Biology Center, Breisacher Str.117, 79106, Freiburg, Germany

    Peter Jantscheff

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  1. Peter Jantscheff
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Correspondence to Peter Jantscheff.

Electronic supplementary material

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10585_2009_9288_MOESM1_ESM.tif

Supplementary Fig. 1 Effect of “orthotopic Co-culture” on CEACAM6 expression of LNCaP cells in vitro. GFP-luciferase fusion protein expressing, CEACAM-negative LNCaP cells were co-cultured in an “orthotopic PCa spheroid in vitro system“with ~ 1-2 mm3 spheroids of normal or PCa prostate tissue (P) for 4 - 21 days in 6-well plates. From individual spheroids epithelial Primary Spheroid Outgrowing Cells (PSOCs) were released into the culture. FACS scatter plots (A) show neither PSOCs from a pure spheroid culture (P90/2), nor GFP expressing, FL1-positive LNCaP cells (LNCaP), do significantly stain with a CEACAM6 specific antibody (9A6). In contrast, two co-cultures of spheroids, PSOCs, and LNCaP (P88/4 ortho and P90/2 ortho) display a striking shift of 10-35% LNCaP cells to CEACAM6 positive cells (right upper quadrant). Histograms (B) gating the GFP-expressing, FL-1 positive LNCaP cells only show a general shift of antigen expression of co-cultered cells (solid and dashed lines) compared to untreated LNCaP cells (black histogram). This shift of antigen expression (also CEACAM 1 is enhanced) was confirmed by staining of co-cultered LNCaP cells with pan-CEACAM (D14-HD11) or anti-CEACAM1 antibodies. In contrast to the “orthotopic Co-culture“DHT-treatment did not change antigen expression (not shown). Whether such changes are also involved in carrier-free implantation of LNCaP cells into mouse prostate tissue was not subject of the present study, but the efficient outgrow of the primary tumors and the strong metastatic spread accompanied by this mode of implantation support such assumptions. The use of luciferase/GFP fusion protein transduced LNCaP cells in the present model, however, will render the possibility to analyze these parameters in the next step [1]. Expression of the two markers not only allows highly sensitive detection of metastatic lesion in different tissues by luciferase in vivo and in vitro (Tab. 1, Fig. 6) but will also give the opportunity to analyze expression of distinct cell surface markers in GFP-expressing metastatic cells by cell flow cytometry in vitro [1]. Additionally it offers the possibility to isolate individual metastatic cells from small tissue-restricted metastases by FACS-sorting and to compare their cellular properties with parental and primary tumor cells (TIFF 3574 kb)

10585_2009_9288_MOESM2_ESM.tif

Supplementary Fig. 2 Tumor localization and delayed re-appearance of tumor growth (1 and 3 no treatment). (A) The figure shows inverted images from 5 min exposure at 10x10 binning before (1, 2) and after (3, 4) treatment (before treatment = time point of randomization; after treatment = final imaging). Three animals were analysed in each imaging set. Strong expansion of tumors (i.e. of luminescence signals) was seen in the vehicle control group (NaCl: iii and iv), whereas the GemLip 8 mg/kg (v) or Gemcitabine 360mg/kg treated groups (iii and vi) showed similar or reduced tumor signals after treatment. Also all other animals with primary imaging signals -despite of exclusion by randomization because of too weak or too strong signals- were also followed up on tumor development. The figure shows one animal (i) which was excluded by randomization from the experiment since it did not show any signal at this time point (1). An imageable tumor, however, developed only at the end of the observation period (3). (B) Figure shows orthotopic tumor localization on the right or left anterior prostate gland (arrows) by the overlay of imaging (5 min exposure at 10x10 binning) on light photographs of SCID mice (overlay corresponding to inverted images in A-4) (TIFF 1110 kb)

10585_2009_9288_MOESM3_ESM.docx

Tab 1supp. Reduction of percentage of animals with metastatic lesions and mean RLU values in different organs of orthotopic PCa models treated with GemLip or Gemc (DOCX 18 kb)

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Jantscheff, P., Ziroli, V., Esser, N. et al. Anti-metastatic effects of liposomal gemcitabine in a human orthotopic LNCaP prostate cancer xenograft model. Clin Exp Metastasis 26, 981–992 (2009). https://doi.org/10.1007/s10585-009-9288-1

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