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Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts.
Cancer Res. 1991 Jul 15; 51(14):3753-61.CR

Abstract

Prostate cancer, the most prevalent cancer affecting men, frequently metastasizes to the axial skeleton where it produces osteoblastic lesions with growth rates often exceeding that of the primary tumor. To evaluate the role of tumor cell-host stromal interaction and stromal specific growth factors (GFs) in prostate cancer growth and progression, we coinoculated athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts s.c. LNCaP tumor formation was most consistently induced by human bone (MS) fibroblasts (62%), followed by embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney, or human lung CCD16 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. The human prostate component of these tumors was confirmed with immunohistochemical staining for prostate-specific antigen (PSA), Northern analysis for PSA expression, and Southern analysis for human repetitive Alu sequences. Elevations in serum PSA paralleled the histomorphological and biochemical findings. LNCaP and fibroblast cell-conditioned media (CM) was used to determine whether autocrine and paracrine mitogenic pathways exist between LNCaP and fibroblast cells in vitro, and various defined GFs were tested to identify possible active factors. Mitogenic assays revealed a 200-300% bidirectional stimulation between LNCaP and bone or prostate fibroblast-derived CM. Lung, normal rat kidney, and 3T3 fibroblast CM were not mitogenic for LNCaP cells. Among the purified GFs tested basic fibroblast growth factor (bFGF) was the most potent mitogen, stimulating LNCaP growth 180% in a concentration-dependent manner. Transforming growth factor alpha and epidermal growth factor were both minimally mitogenic. Coinoculation of LNCaP cells with a slowly absorbed matrix (Gelfoam) absorbed with bFGF or dialyzed and concentrated rUGM or MS CM was also capable of inducing LNCaP tumor formation in vivo. These observations illustrate that fibroblasts differentially modulate prostate cancer growth through the release of paracrine-mediated GFs, possibly including bFGF, and that tumor-stromal cell interactions play an important role in prostate cancer growth and progression.

Authors+Show Affiliations

Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston 77030.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1712249

Citation

Gleave, M, et al. "Acceleration of Human Prostate Cancer Growth in Vivo By Factors Produced By Prostate and Bone Fibroblasts." Cancer Research, vol. 51, no. 14, 1991, pp. 3753-61.
Gleave M, Hsieh JT, Gao CA, et al. Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Res. 1991;51(14):3753-61.
Gleave, M., Hsieh, J. T., Gao, C. A., von Eschenbach, A. C., & Chung, L. W. (1991). Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Research, 51(14), 3753-61.
Gleave M, et al. Acceleration of Human Prostate Cancer Growth in Vivo By Factors Produced By Prostate and Bone Fibroblasts. Cancer Res. 1991 Jul 15;51(14):3753-61. PubMed PMID: 1712249.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. AU - Gleave,M, AU - Hsieh,J T, AU - Gao,C A, AU - von Eschenbach,A C, AU - Chung,L W, PY - 1991/7/15/pubmed PY - 1991/7/15/medline PY - 1991/7/15/entrez SP - 3753 EP - 61 JF - Cancer research JO - Cancer Res VL - 51 IS - 14 N2 - Prostate cancer, the most prevalent cancer affecting men, frequently metastasizes to the axial skeleton where it produces osteoblastic lesions with growth rates often exceeding that of the primary tumor. To evaluate the role of tumor cell-host stromal interaction and stromal specific growth factors (GFs) in prostate cancer growth and progression, we coinoculated athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts s.c. LNCaP tumor formation was most consistently induced by human bone (MS) fibroblasts (62%), followed by embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney, or human lung CCD16 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. The human prostate component of these tumors was confirmed with immunohistochemical staining for prostate-specific antigen (PSA), Northern analysis for PSA expression, and Southern analysis for human repetitive Alu sequences. Elevations in serum PSA paralleled the histomorphological and biochemical findings. LNCaP and fibroblast cell-conditioned media (CM) was used to determine whether autocrine and paracrine mitogenic pathways exist between LNCaP and fibroblast cells in vitro, and various defined GFs were tested to identify possible active factors. Mitogenic assays revealed a 200-300% bidirectional stimulation between LNCaP and bone or prostate fibroblast-derived CM. Lung, normal rat kidney, and 3T3 fibroblast CM were not mitogenic for LNCaP cells. Among the purified GFs tested basic fibroblast growth factor (bFGF) was the most potent mitogen, stimulating LNCaP growth 180% in a concentration-dependent manner. Transforming growth factor alpha and epidermal growth factor were both minimally mitogenic. Coinoculation of LNCaP cells with a slowly absorbed matrix (Gelfoam) absorbed with bFGF or dialyzed and concentrated rUGM or MS CM was also capable of inducing LNCaP tumor formation in vivo. These observations illustrate that fibroblasts differentially modulate prostate cancer growth through the release of paracrine-mediated GFs, possibly including bFGF, and that tumor-stromal cell interactions play an important role in prostate cancer growth and progression. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/1712249/Acceleration_of_human_prostate_cancer_growth_in_vivo_by_factors_produced_by_prostate_and_bone_fibroblasts_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=1712249 DB - PRIME DP - Unbound Medicine ER -