| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Departments of Pathology and Urology,*
Weill
Medical College of Cornell University and the New York Presbyterian
Hospital, New York, New York; and the Van Andel Research
Institute,
Grand Rapids, Michigan
Hepatocyte growth factor/scatter factor (HGF/SF) promotes the proliferation, differentiation, motility, and invasion of epithelial cells by binding to its cell surface receptor, the Met tyrosine kinase. In the prostate, Met is expressed predominantly by prostate epithelial cells (PrEC), whereas HGF/SF is synthesized by prostate stromal cells (PrSC). Met is also expressed in localized and metastatic prostate cancers. Our results show that PrECs in in vitro culture maintain expression of Met at a level comparable to DU145 cancer cell expression. HGF/SF secreted by PrSC stimulates tyrosine phosphorylation of the Met receptor. In normal PrEC, HGF/SF causes growth inhibition, sustained phosphorylation of mitogen-activated protein kinase, and increased CK18 expression consistent with cell differentiation. In contrast, HGF/SF significantly stimulates the proliferation of DU145 prostate cancer cells. HGF/SF in the conditioned medium of PrSC specifically induces migration of both normal and malignant prostate epithelial cells through MatriGel-coated Transwell filters. HGF/SF depletion reduces cell migration by approximately 50%. The response of PrEC is specific for HGF/SF since the other growth factors tested do not significantly affect growth or migration of PrECs. These results support the in vivo importance of the prostate stroma and specifically of HGF/SF as a unique stromal derived factor in the development and progression of prostate cancer.
This article has been cited by other articles:
 |
|
 |
|
  L. E. Lamb, B. S. Knudsen, and C. K. Miranti E-cadherin-mediated survival of androgen-receptor-expressing secretory prostate epithelial cells derived from a stratified in vitro differentiation model J. Cell Sci., January 15, 2010; 123(2): 266 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gupta, P. I. Karakiewicz, C. G. Roehrborn, Y. Lotan, A. R. Zlotta, and S. F. Shariat Predictive Value of Plasma Hepatocyte Growth Factor/Scatter Factor Levels in Patients with Clinically Localized Prostate Cancer Clin. Cancer Res., November 15, 2008; 14(22): 7385 - 7390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Edick, L. Tesfay, L. E. Lamb, B. S. Knudsen, and C. K. Miranti Inhibition of Integrin-mediated Crosstalk with Epidermal Growth Factor Receptor/Erk or Src Signaling Pathways in Autophagic Prostate Epithelial Cells Induces Caspase-independent Death Mol. Biol. Cell, July 1, 2007; 18(7): 2481 - 2490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. O'Connor, M. C. Farach-Carson, C. J. Schneider, and D. D. Carson Coculture with Prostate Cancer Cells Alters Endoglin Expression and Attenuates Transforming Growth Factor-{beta} Signaling in Reactive Bone Marrow Stromal Cells Mol. Cancer Res., June 1, 2007; 5(6): 585 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bavik, I. Coleman, J. P. Dean, B. Knudsen, S. Plymate, and P. S. Nelson The Gene Expression Program of Prostate Fibroblast Senescence Modulates Neoplastic Epithelial Cell Proliferation through Paracrine Mechanisms Cancer Res., January 15, 2006; 66(2): 794 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Knudsen, J. M. Lucas, L. Fazli, S. Hawley, S. Falcon, I. M. Coleman, D. B. Martin, C. Xu, L. D. True, M. E. Gleave, et al. Regulation of Hepatocyte Activator Inhibitor-1 Expression by Androgen and Oncogenic Transformation in the Prostate Am. J. Pathol., July 1, 2005; 167(1): 255 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Shinomiya, C. F. Gao, Q. Xie, M. Gustafson, D. J. Waters, Y.-W. Zhang, and G. F. Vande Woude RNA Interference Reveals that Ligand-Independent Met Activity Is Required for Tumor Cell Signaling and Survival Cancer Res., November 1, 2004; 64(21): 7962 - 7970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Bill, B. Knudsen, S. L. Moores, S. K. Muthuswamy, V. R. Rao, J. S. Brugge, and C. K. Miranti Epidermal Growth Factor Receptor-Dependent Regulation of Integrin-Mediated Signaling and Cell Cycle Entry in Epithelial Cells Mol. Cell. Biol., October 1, 2004; 24(19): 8586 - 8599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Shinomiya and G. F. Vande Woude Suppression of Met Expression: A Possible Cancer Treatment: Commentary re: S. J. Kim et al., Reduced c-Met Expression by an Adenovirus Expressing a c-Met Ribozyme Inhibits Tumorigenic Growth and Lymph Node Metastases of PC3-LN4 Prostate Tumor Cells in an Orthotopic Nude Mouse Model. Clin. Cancer Res., 14: 5161-5170, 2003. Clin. Cancer Res., November 1, 2003; 9(14): 5085 - 5090. [Full Text] [PDF]
|
|
|
|
|
|
S. J. Kim, M. Johnson, K. Koterba, M. H. Herynk, H. Uehara, and G. E. Gallick Reduced c-Met Expression by an Adenovirus Expressing a c-Met Ribozyme Inhibits Tumorigenic Growth and Lymph Node Metastases of PC3-LN4 Prostate Tumor Cells in an Orthotopic Nude Mouse Model Clin. Cancer Res., November 1, 2003; 9(14): 5161 - 5170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. V. Litvinov, A. M. De Marzo, and J. T. Isaacs Is the Achilles' Heel for Prostate Cancer Therapy a Gain of Function in Androgen Receptor Signaling? J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 2972 - 2982. [Full Text] [PDF]
|
|
|
|
|
|
G. J. L. H. van Leenders, W. R. Gage, J. L. Hicks, B. van Balken, T. W. Aalders, J. A. Schalken, and A. M. De Marzo Intermediate Cells in Human Prostate Epithelium Are Enriched in Proliferative Inflammatory Atrophy Am. J. Pathol., May 1, 2003; 162(5): 1529 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V.-M. Wasenius, S. Hemmer, E. Kettunen, S. Knuutila, K. Franssila, and H. Joensuu Hepatocyte Growth Factor Receptor, Matrix Metalloproteinase-11, Tissue Inhibitor of Metalloproteinase-1, and Fibronectin Are Up-Regulated in Papillary Thyroid Carcinoma: A cDNA and Tissue Microarray Study Clin. Cancer Res., January 1, 2003; 9(1): 68 - 75. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
