Human prostate cancer model: Roles of growth factors and extracellular matrices

L. W K Chung, W. Li, M. E. Gleave, J. T. Hsieh, H. C. Wu, R. A. Sikes, H. E. Zhau, M. G. Bandyk, C. J. Logothetis, J. S. Rubin, A. C. Von Eschenbach

Research output: Contribution to journalArticle

Abstract

A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam®. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone-conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGFβ, IGF1, IGF2, PDGF, EGF, TGFα and KGF, stimulated anchorage-independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV. None of the ECM proteins induced soft agar colony formation by normal prostate epithelial cells. Therefore, it is possible that the ECM protein(s) may potentiate the tumor-inducing activity of locally produced GFs.

Original languageEnglish (US)
Pages (from-to)99-105
Number of pages7
JournalJournal of Cellular Biochemistry
Volume50
Issue numberSUPPL. H
DOIs
StatePublished - 1992

Fingerprint

Extracellular Matrix
Tumors
Prostatic Neoplasms
Intercellular Signaling Peptides and Proteins
Bone
Bone and Bones
Prostate
Extracellular Matrix Proteins
Prostate-Specific Antigen
Conditioned Culture Medium
Agar
Neoplasms
Growth
Cells
Absorbable Gelatin Sponge
Affinity chromatography
Tenascin
Cell Line
Column chromatography
Dithiothreitol

Keywords

  • bFGF
  • extracellular matrices (ECMs)
  • growth factors (GFs)
  • HGF and KGF
  • human prostate cancer model
  • NGF
  • prostate cancer-bone interaction
  • stromal-epithelial interaction

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Chung, L. W. K., Li, W., Gleave, M. E., Hsieh, J. T., Wu, H. C., Sikes, R. A., ... Von Eschenbach, A. C. (1992). Human prostate cancer model: Roles of growth factors and extracellular matrices. Journal of Cellular Biochemistry, 50(SUPPL. H), 99-105. https://doi.org/10.1002/jcb.240501222

Human prostate cancer model : Roles of growth factors and extracellular matrices. / Chung, L. W K; Li, W.; Gleave, M. E.; Hsieh, J. T.; Wu, H. C.; Sikes, R. A.; Zhau, H. E.; Bandyk, M. G.; Logothetis, C. J.; Rubin, J. S.; Von Eschenbach, A. C.

In: Journal of Cellular Biochemistry, Vol. 50, No. SUPPL. H, 1992, p. 99-105.

Research output: Contribution to journalArticle

Chung, LWK, Li, W, Gleave, ME, Hsieh, JT, Wu, HC, Sikes, RA, Zhau, HE, Bandyk, MG, Logothetis, CJ, Rubin, JS & Von Eschenbach, AC 1992, 'Human prostate cancer model: Roles of growth factors and extracellular matrices', Journal of Cellular Biochemistry, vol. 50, no. SUPPL. H, pp. 99-105. https://doi.org/10.1002/jcb.240501222
Chung, L. W K ; Li, W. ; Gleave, M. E. ; Hsieh, J. T. ; Wu, H. C. ; Sikes, R. A. ; Zhau, H. E. ; Bandyk, M. G. ; Logothetis, C. J. ; Rubin, J. S. ; Von Eschenbach, A. C. / Human prostate cancer model : Roles of growth factors and extracellular matrices. In: Journal of Cellular Biochemistry. 1992 ; Vol. 50, No. SUPPL. H. pp. 99-105.
@article{b8352a16548d4f7891a439920e78ddd5,
title = "Human prostate cancer model: Roles of growth factors and extracellular matrices",
abstract = "A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam{\circledR}. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone-conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGFβ, IGF1, IGF2, PDGF, EGF, TGFα and KGF, stimulated anchorage-independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV. None of the ECM proteins induced soft agar colony formation by normal prostate epithelial cells. Therefore, it is possible that the ECM protein(s) may potentiate the tumor-inducing activity of locally produced GFs.",
keywords = "bFGF, extracellular matrices (ECMs), growth factors (GFs), HGF and KGF, human prostate cancer model, NGF, prostate cancer-bone interaction, stromal-epithelial interaction",
author = "Chung, {L. W K} and W. Li and Gleave, {M. E.} and Hsieh, {J. T.} and Wu, {H. C.} and Sikes, {R. A.} and Zhau, {H. E.} and Bandyk, {M. G.} and Logothetis, {C. J.} and Rubin, {J. S.} and {Von Eschenbach}, {A. C.}",
year = "1992",
doi = "10.1002/jcb.240501222",
language = "English (US)",
volume = "50",
pages = "99--105",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "SUPPL. H",

}

TY - JOUR

T1 - Human prostate cancer model

T2 - Roles of growth factors and extracellular matrices

AU - Chung, L. W K

AU - Li, W.

AU - Gleave, M. E.

AU - Hsieh, J. T.

AU - Wu, H. C.

AU - Sikes, R. A.

AU - Zhau, H. E.

AU - Bandyk, M. G.

AU - Logothetis, C. J.

AU - Rubin, J. S.

AU - Von Eschenbach, A. C.

PY - 1992

Y1 - 1992

N2 - A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam®. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone-conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGFβ, IGF1, IGF2, PDGF, EGF, TGFα and KGF, stimulated anchorage-independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV. None of the ECM proteins induced soft agar colony formation by normal prostate epithelial cells. Therefore, it is possible that the ECM protein(s) may potentiate the tumor-inducing activity of locally produced GFs.

AB - A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam®. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone-conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGFβ, IGF1, IGF2, PDGF, EGF, TGFα and KGF, stimulated anchorage-independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV. None of the ECM proteins induced soft agar colony formation by normal prostate epithelial cells. Therefore, it is possible that the ECM protein(s) may potentiate the tumor-inducing activity of locally produced GFs.

KW - bFGF

KW - extracellular matrices (ECMs)

KW - growth factors (GFs)

KW - HGF and KGF

KW - human prostate cancer model

KW - NGF

KW - prostate cancer-bone interaction

KW - stromal-epithelial interaction

UR - http://www.scopus.com/inward/record.url?scp=0027097819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027097819&partnerID=8YFLogxK

U2 - 10.1002/jcb.240501222

DO - 10.1002/jcb.240501222

M3 - Article

C2 - 1289680

VL - 50

SP - 99

EP - 105

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - SUPPL. H

ER -