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 cell with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam®. The resulting LNCaP tumors were used to evaluate PSA production and excretion 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 NaCI‐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 a FGF, 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. © 1992 Wiley‐Liss, Inc.
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 cell with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam®. The resulting LNCaP tumors were used to evaluate PSA production and excretion 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 NaCI‐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 a FGF, 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. © 1992 Wiley‐Liss, Inc.
KW - HGF and KGF
KW - NGF
KW - bFGF
KW - extracellular matrices (ECMs)
KW - growth factors (GFs)
KW - human prostate cancer model
KW - prostate cancer‐bone interaction
KW - stromal‐epithelial interaction
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U2 - 10.1002/jcb.240501222
DO - 10.1002/jcb.240501222
M3 - Article
C2 - 1289680
AN - SCOPUS:0027034299
SN - 0730-2312
VL - 50
SP - 99
EP - 105
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - S16H
ER -