Characterization of nerve growth factor precursor protein expression by human prostate stromal cells: A role in selective neurotrophin stimulation of prostate epithelial cell growth

Delsite, Robert; Djakiew, Daniel

doi:10.1002/(sici)1097-0045(19990915)41:1<39::aid-pros6>3.0.co;2-e

Cited by 43 publications

(32 citation statements)

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“…NGF-β stimulates the growth of prostate epithelial cells, which suggests the paracrine regulation of prostate cell growth by NGF-β or other neurotrophins. In contrast to benign prostate epithelial cells, p75NTR expression is decreased in cancer cells (13,14). A dramatic increase in p75 immunoreactivity has been observed in the stroma and this correlates with an increase in malignancy (16).…”

Section: Introductionmentioning

confidence: 91%

“…Neurotrophin growth factor [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5)] binding activates tyrosine kinase receptors encoded by the Trk family (Trk A, Trk B and Trk C), and the low-affinity receptor p75NTR. In the normal prostate, p75NTR and Trk A are found on benign prostate epithelial cells, whereas NGF-β is expressed by adjacent stromal cells (13)(14)(15)(16). NGF-β stimulates the growth of prostate epithelial cells, which suggests the paracrine regulation of prostate cell growth by NGF-β or other neurotrophins.…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples

Gravina

Mancini

Ranieri

et al. 2013

International Journal of Oncology

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Abstract.Emerging evidence has shown that the tumor microenvironment plays a crucial role in prostate cancer (PCa) development and progression. However, the mechanism(s) through which stromal cells regulate epithelial cells and the differences among prostatic stromal cells of different histological/pathological origin in PCa progression remain unclear. Therefore, it is necessary to characterize the stromal cell populations present in benign prostatic hyperplasia (BPH) and PCa. To this end, we used cultures from stromal cells obtained from BPH-derived (15 cases) and PCa-derived (30 cases) primary cultures. In culture, stromal cells are a mixture of fibroblasts, myofibroblasts (MFs) and muscle cells. Fibroblasts are characterized for the expression of vimentin, MFs for the co-expression of α-smooth muscle actin (α-SMA) and vimentin, whereas muscle cells for the expression of α-SMA and desmin. Fibroblasts were present in large amounts in the BPH-compared to the PCa-derived cultures, whereas MFs were more representative of PCa-as opposed to BPH-derived cultures. Some α-SMA-positive cells retained the expression of basal cytokeratin K14. This population was defined as myoepithelial cells and was associated with senescent cultures. The percentage of MFs was higher in high-grade compared to moderate-and low-grade PCa-derived cultures, whereas the number of myoepithelial cells was lower in high-grade compared to moderate-and low-grade PCa-derived cultures. In addition, we analyzed the expression of p75NTR, as well as the expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of MMPs (TIMPs). p75NTR expression was elevated in the stromal cultures derived from PCa compared to those derived from BPH and in cultures derived from cases with Gleason scores ≥7 compared to those derived from cases with Gleason scores <7, as well as in cultures with a high concentration of MFs compared to those with a high concentration of fibroblasts. MMP-2 was secreted by all primary cultures, whereas MMP-9 secretion was observed only in some PCa-derived stromal cells, when the percentage of MFs was significantly higher compared to BPH-derived cultures. TIMP1, TIMP2 and TIMP3 were secreted in elevated amounts in the BPH-compared to the PCa-derived stromal cultures, suggesting the differential regulation of extracellular matrix (ECM) degradation. When we used 22rv1 and PC3 PCa xenograft models for the isolation and characterization of murine cancer-associated fibroblasts (CAFs) we noted that the angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, vimentin, tenascin, calponin, desmin and Masson's trichrome. In conclusion, MF stromal cells from PCa participate in the progression and metastasis of PCa, modualting inflammation, angiogenesis and epithelial cancer cell proliferation.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples

Gravina

Mancini

Ranieri

et al. 2013

International Journal of Oncology

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“…33 Secretions from prostate stromal cells are able to induce chemotaxis and chemokinesis of TSU-pr1, PC-3 and DU-145 prostate tumor cell lines in a modified Boyden chamber assay. 34 These secretions contain many proteins, including an NGF precursor, 35 which upon immunoprecipitation inhibits chemotaxis of the tumor cells. 34 Indeed, recombinant NGF also increases the invasive capability of prostate cancer cells in vitro.…”

Section: Increased P75 Ntr Expression Suppresses Ngf-stimulated Satelmentioning

confidence: 99%

Neurotrophin receptor p75^NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells

Krygier

Djakiew

2001

Intl Journal of Cancer

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The loss of tumor-and/or metastasis-suppressor gene function contributes to the transformation of human prostate epithelial cells to a malignant pathology. Such a putative tumor-suppressor and metastasis-suppressor gene(s) has been mapped to the region of 17q21, which coincidentally is in the vicinity of the human gene locus for the neurotrophin receptor p75 NTR . The p75 NTR is expressed in normal human prostate epithelial cells and exhibits an inverse association of p75 NTR expression with the malignant progression of the prostate, consistent with a pathologic role of the p75 NTR as a putative tumor and metastasis suppressor. Utilizing stable transfectants of the TSU-pr1 and PC-3 human prostate tumor cell lines that exhibit a rank order (dose-dependent) increase in p75 NTR protein expression, we investigated the effects of the p75 NTR in combination with its predominant ligand, nerve growth factor (NGF), on tumor cell growth. A rank order (dose-dependent) increase in p75 NTR expression was found to suppress the growth of prostate tumors in severe combined immunodeficient (SCID) mice. Treatment of these tumors with NGF stimulated both proliferation as indicated by PCNA expression and apoptosis as indicated by TUNEL assay, the net result of which was no change in the overall growth of the tumors. However, NGF was found to increase the formation of satellite tumors, both contiguous and noncontiguous with respect to the primary tumor mass, indicating dose-dependent induction of metastasis. Significantly, the formation of satellite tumors was suppressed by the expression of p75 NTR . This suggests that p75 NTR is a tumor suppressor of growth and a metastasis suppressor of NGF-stimulated migration of human prostate tumor cells.

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“…sympathetic neurons (16) and dorsal root ganglia (17)) but by many different tissues outside the nervous system. These include cells of the ovary (18 -20), bone marrow (21), hair follicles (22), liver (23), urinary bladder (24), retina (25), prostate cells (26), oral mucosal keratinocytes (27), and spermatids (28). NGF is also produced and released by cells of the immune system, namely mast cells, which also respond to NGF (29,30).…”

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confidence: 88%

Human Tryptase Cleaves Pro-Nerve Growth Factor (Pro-NGF)

Spinnler

Fröhlich

Arnold

et al. 2011

Journal of Biological Chemistry

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Characterization of nerve growth factor precursor protein expression by human prostate stromal cells: A role in selective neurotrophin stimulation of prostate epithelial cell growth

Cited by 43 publications

References 30 publications

Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples

Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples

Neurotrophin receptor p75^NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells

Human Tryptase Cleaves Pro-Nerve Growth Factor (Pro-NGF)

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Characterization of nerve growth factor precursor protein expression by human prostate stromal cells: A role in selective neurotrophin stimulation of prostate epithelial cell growth

Cited by 43 publications

References 30 publications

Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples

Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples

Neurotrophin receptor p75NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells

Human Tryptase Cleaves Pro-Nerve Growth Factor (Pro-NGF)

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Neurotrophin receptor p75^NTR suppresses growth and nerve growth factor‐mediated metastasis of human prostate cancer cells