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Prostate carcinoma cells that have resided in bone have an upregulated IGF-I axis.
Prostate. 2004 Jan 01; 58(1):41-9.P

Abstract

BACKGROUND

Prostate cancer (PC) has a propensity to metastasize to the skeleton, inducing an osteoblastic response in the host. Recent epidemiological studies have suggested that circulating IGF-I may be important for both the pathogenesis and dissemination of PC. We have postulated that tumor secreted IGF-I in conjunction with endogenous IGF-I contributes to the osteoblastic phenotype characteristic of metastatic PC.

METHODS

To test this thesis we studied the established LNCaP PC progression model consisting of three genetically related human PC cell lines.

RESULTS

Using RIA, we found serum-free conditioned media (CM) of LNCaP and C4-2 had no measurable IGF-I, whereas IGF-I was easily detected in CM from C4-2B cells at 24 hr (i.e., 1.8 +/- 0.53 ng/mg cell protein). Real-time PCR of IGF-I mRNA showed that C4-2B expressed 100-fold more IGF-I mRNA than LNCaP cells. In addition, C4-2B expression of IGF-I mRNA was substantially increased in the presence of exogenous IGF-I to nearly twofold. While IGFBP-3 and IGFBP-1 were not detectable in the CM of any PC line, all cells secreted IGFBP-2. C4-2B cells produced 40% more IGFBP-2 than LNCaP or C4-2 cells (C4-2B at 167 +/- 43 ng/mg cell protein). RANKL, a product of bone stromal cells, was also differentially expressed: LNCaP had threefold higher RANKL mRNA compared to C4-2 and C4-2B and at least equivalent protein expression.

CONCLUSIONS

Our results suggest that PC cells that have metastasized to bone have an upregulated IGF-I regulatory system. This suggests an activated IGF-I axis contributes to the host-PC interaction in promoting osteoblastic metastases.

Authors+Show Affiliations

Department of Medicine, VAMC and Emory University, Atlanta, Georgia 30033, USA. jrubin02@emory.eduNo affiliation info availableNo affiliation info availableNo 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

14673951

Citation

Rubin, J, et al. "Prostate Carcinoma Cells That Have Resided in Bone Have an Upregulated IGF-I Axis." The Prostate, vol. 58, no. 1, 2004, pp. 41-9.
Rubin J, Chung LW, Fan X, et al. Prostate carcinoma cells that have resided in bone have an upregulated IGF-I axis. Prostate. 2004;58(1):41-9.
Rubin, J., Chung, L. W., Fan, X., Zhu, L., Murphy, T. C., Nanes, M. S., & Rosen, C. J. (2004). Prostate carcinoma cells that have resided in bone have an upregulated IGF-I axis. The Prostate, 58(1), 41-9.
Rubin J, et al. Prostate Carcinoma Cells That Have Resided in Bone Have an Upregulated IGF-I Axis. Prostate. 2004 Jan 1;58(1):41-9. PubMed PMID: 14673951.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prostate carcinoma cells that have resided in bone have an upregulated IGF-I axis. AU - Rubin,J, AU - Chung,L W K, AU - Fan,X, AU - Zhu,L, AU - Murphy,T C, AU - Nanes,M S, AU - Rosen,C J, PY - 2003/12/16/pubmed PY - 2004/2/6/medline PY - 2003/12/16/entrez SP - 41 EP - 9 JF - The Prostate JO - Prostate VL - 58 IS - 1 N2 - BACKGROUND: Prostate cancer (PC) has a propensity to metastasize to the skeleton, inducing an osteoblastic response in the host. Recent epidemiological studies have suggested that circulating IGF-I may be important for both the pathogenesis and dissemination of PC. We have postulated that tumor secreted IGF-I in conjunction with endogenous IGF-I contributes to the osteoblastic phenotype characteristic of metastatic PC. METHODS: To test this thesis we studied the established LNCaP PC progression model consisting of three genetically related human PC cell lines. RESULTS: Using RIA, we found serum-free conditioned media (CM) of LNCaP and C4-2 had no measurable IGF-I, whereas IGF-I was easily detected in CM from C4-2B cells at 24 hr (i.e., 1.8 +/- 0.53 ng/mg cell protein). Real-time PCR of IGF-I mRNA showed that C4-2B expressed 100-fold more IGF-I mRNA than LNCaP cells. In addition, C4-2B expression of IGF-I mRNA was substantially increased in the presence of exogenous IGF-I to nearly twofold. While IGFBP-3 and IGFBP-1 were not detectable in the CM of any PC line, all cells secreted IGFBP-2. C4-2B cells produced 40% more IGFBP-2 than LNCaP or C4-2 cells (C4-2B at 167 +/- 43 ng/mg cell protein). RANKL, a product of bone stromal cells, was also differentially expressed: LNCaP had threefold higher RANKL mRNA compared to C4-2 and C4-2B and at least equivalent protein expression. CONCLUSIONS: Our results suggest that PC cells that have metastasized to bone have an upregulated IGF-I regulatory system. This suggests an activated IGF-I axis contributes to the host-PC interaction in promoting osteoblastic metastases. SN - 0270-4137 UR - https://www.unboundmedicine.com/medline/citation/14673951/Prostate_carcinoma_cells_that_have_resided_in_bone_have_an_upregulated_IGF_I_axis_ L2 - https://doi.org/10.1002/pros.10299 DB - PRIME DP - Unbound Medicine ER -