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. 2000 Feb;82(4):990–997. doi: 10.1054/bjoc.1999.1029

In vitro modelling of epithelial and stromal interactions in non-malignant and malignant prostates

S H Lang 1, M Stower 2, N J Maitland 1
PMCID: PMC2374381  PMID: 10732776

Abstract

To study the effects of stromal epithelial cell interactions on prostate cancer metastasis, we have used primary human prostatic stromal cells derived from malignant and non-malignant tissues and established epithelial cell lines from normal (PNT1a and PNT2-C2) and tumour (PC-3, DU145 and LNCaP) origins. The effects of stromal cells on epithelial cell growth were studied in direct and indirect (using culture inserts) co-culture and by exposure to stromal cell-conditioned medium (assessed by MTT assay). The influence of stromal cells on epithelial cell invasion was measured using matrigel invasion chambers and on epithelial cell motility using time lapse microscopy. Results indicated that epithelial cell line growth was similarly unaffected or inhibited by stromal cells derived from malignant (n = 8) or non-malignant tissue (n = 8). In contrast, PNT2-C2 and PC-3 cells were found to be the least and the most invasive and motile epithelia respectively. Stromal cultures enhanced the invasion of both epithelial cells, but no differences were observed between the use of malignant and non-malignant tissues. All stromal cultures modestly stimulated PNT2-C2 motility but displayed a greater stimulation of PC-3 cell motility, while stromal cells derived from malignant tissue stimulated PNT2-C2 and PC-3 cell motility more than stromal cultures from non-malignant tissues. © 2000 Cancer Research Campaign

Keywords: prostate cancer, epithelia–stroma interactions

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Selected References

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  1. Atula S., Grenman R., Syrjänen S. Fibroblasts can modulate the phenotype of malignant epithelial cells in vitro. Exp Cell Res. 1997 Aug 25;235(1):180–187. doi: 10.1006/excr.1997.3676. [DOI] [PubMed] [Google Scholar]
  2. Camps J. L., Chang S. M., Hsu T. C., Freeman M. R., Hong S. J., Zhau H. E., von Eschenbach A. C., Chung L. W. Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. Proc Natl Acad Sci U S A. 1990 Jan;87(1):75–79. doi: 10.1073/pnas.87.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Degeorges A., Tatoud R., Fauvel-Lafeve F., Podgorniak M. P., Millot G., de Cremoux P., Calvo F. Stromal cells from human benign prostate hyperplasia produce a growth-inhibitory factor for LNCaP prostate cancer cells, identified as interleukin-6. Int J Cancer. 1996 Oct 9;68(2):207–214. doi: 10.1002/(SICI)1097-0215(19961009)68:2<207::AID-IJC12>3.0.CO;2-7. [DOI] [PubMed] [Google Scholar]
  4. Dijkman G. A., Debruyne F. M. Epidemiology of prostate cancer. Eur Urol. 1996;30(3):281–295. doi: 10.1159/000474185. [DOI] [PubMed] [Google Scholar]
  5. Gleave M., Hsieh J. T., Gao C. A., von Eschenbach A. C., Chung L. W. Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Res. 1991 Jul 15;51(14):3753–3761. [PubMed] [Google Scholar]
  6. Hayward S. W., Rosen M. A., Cunha G. R. Stromal-epithelial interactions in the normal and neoplastic prostate. Br J Urol. 1997 Apr;79 (Suppl 2):18–26. doi: 10.1111/j.1464-410x.1997.tb16917.x. [DOI] [PubMed] [Google Scholar]
  7. Heylen N., Baurain R., Remacle C., Trouet A. Effect of MRC-5 fibroblast conditioned medium on breast cancer cell motility and invasion in vitro. Clin Exp Metastasis. 1998 Feb;16(2):193–203. doi: 10.1023/a:1006532523152. [DOI] [PubMed] [Google Scholar]
  8. Ito A., Nakajima S., Sasaguri Y., Nagase H., Mori Y. Co-culture of human breast adenocarcinoma MCF-7 cells and human dermal fibroblasts enhances the production of matrix metalloproteinases 1, 2 and 3 in fibroblasts. Br J Cancer. 1995 May;71(5):1039–1045. doi: 10.1038/bjc.1995.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kabalin J. N., Peehl D. M., Stamey T. A. Clonal growth of human prostatic epithelial cells is stimulated by fibroblasts. Prostate. 1989;14(3):251–263. doi: 10.1002/pros.2990140306. [DOI] [PubMed] [Google Scholar]
  10. Kooistra A., Elissen N. M., König J. J., Vermey M., van der Kwast T. H., Romijn J. C., Schröder F. H. Immunocytochemical characterization of explant cultures of human prostatic stromal cells. Prostate. 1995 Jul;27(1):42–49. doi: 10.1002/pros.2990270108. [DOI] [PubMed] [Google Scholar]
  11. Kooistra A., van den Eijnden-van Raaij A. J., Klaij I. A., Romijn J. C., Schröder F. H. Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta. Br J Cancer. 1995 Aug;72(2):427–434. doi: 10.1038/bjc.1995.350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. König J. J., Romijn J. C., Schröder F. H. Prostatic epithelium inhibiting factor (PEIF): organ specificity and production by prostatic fibroblasts. Urol Res. 1987;15(3):145–149. doi: 10.1007/BF00254426. [DOI] [PubMed] [Google Scholar]
  13. Lang S. H., Clarke N. W., George N. J., Allen T. D., Testa N. G. Interaction of prostate epithelial cells from benign and malignant tumor tissue with bone-marrow stroma. Prostate. 1998 Feb 15;34(3):203–213. doi: 10.1002/(sici)1097-0045(19980215)34:3<203::aid-pros8>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  14. Macintosh C. A., Stower M., Reid N., Maitland N. J. Precise microdissection of human prostate cancers reveals genotypic heterogeneity. Cancer Res. 1998 Jan 1;58(1):23–28. [PubMed] [Google Scholar]
  15. Mohler J. L., Partin A. W., Isaacs J. T., Coffey D. S. Metastatic potential prediction by a visual grading system of cell motility: prospective validation in the Dunning R-3327 prostatic adenocarcinoma model. Cancer Res. 1988 Aug 1;48(15):4312–4317. [PubMed] [Google Scholar]
  16. Nakamura T., Matsumoto K., Kiritoshi A., Tano Y., Nakamura T. Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells: in vitro analysis of tumor-stromal interactions. Cancer Res. 1997 Aug 1;57(15):3305–3313. [PubMed] [Google Scholar]
  17. Noël A., Hajitou A., L'Hoir C., Maquoi E., Baramova E., Lewalle J. M., Remacle A., Kebers F., Brown P., Calberg-Bacq C. M. Inhibition of stromal matrix metalloproteases: effects on breast-tumor promotion by fibroblasts. Int J Cancer. 1998 Apr 13;76(2):267–273. doi: 10.1002/(sici)1097-0215(19980413)76:2<267::aid-ijc15>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  18. Pasternack M., Jr, Liu X., Goodman R. A., Rannels D. E. Regulated stimulation of epithelial cell DNA synthesis by fibroblast-derived mediators. Am J Physiol. 1997 Apr;272(4 Pt 1):L619–L630. doi: 10.1152/ajplung.1997.272.4.L619. [DOI] [PubMed] [Google Scholar]
  19. Ropiquet F., Huguenin S., Villette J. M., Ronflé V., Le Brun G., Maitland N. J., Cussenot O., Fiet J., Berthon P. FGF7/KGF triggers cell transformation and invasion on immortalised human prostatic epithelial PNT1A cells. Int J Cancer. 1999 Jul 19;82(2):237–243. doi: 10.1002/(sici)1097-0215(19990719)82:2<237::aid-ijc14>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  20. Schor S. L., Schor A. M., Grey A. M., Rushton G. Foetal and cancer patient fibroblasts produce an autocrine migration-stimulating factor not made by normal adult cells. J Cell Sci. 1988 Jul;90(Pt 3):391–399. doi: 10.1242/jcs.90.3.391. [DOI] [PubMed] [Google Scholar]
  21. van Roozendaal K. E., Klijn J. G., van Ooijen B., Claassen C., Eggermont A. M., Henzen-Logmans S. C., Foekens J. A. Differential regulation of breast tumor cell proliferation by stromal fibroblasts of various breast tissue sources. Int J Cancer. 1996 Jan 3;65(1):120–125. doi: 10.1002/(SICI)1097-0215(19960103)65:1<120::AID-IJC20>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]

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