Osteoblasts induce prostate cancer proliferation and PSA expression through interleukin-6-mediated activation of the androgen receptor

Lü, Yi; Zhang, Jian; Dai, Jinlu; Dehne, Lindsay A.; Mizokami, Atsushi; Yao, Zhi; Keller, Evan T.

doi:10.1007/s10585-005-0056-6

Cited by 56 publications

(51 citation statements)

References 42 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, the BMP-induced osteoblastogenesis may make the bone microenvironment favorable for the establishment of prostate cancer metastases, which would account for the predisposition of prostate cancer metastases to bone (53). Osteoblasts produce a variety of factors such as transforming growth factor-h and interleukin-6 that may promote prostate cancer progression (54)(55)(56)(57)(58)(59)(60). Thus, if BMPs promote osteoblastogenesis, Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Bone Morphogenetic Protein-6 Promotes Osteoblastic Prostate Cancer Bone Metastases through a Dual Mechanism

et al. 2005

Self Cite

View full text Add to dashboard Cite

Prostate cancer frequently metastasizes to bone where it forms osteoblastic lesions through unknown mechanisms. Bone morphogenetic proteins (BMP) are mediators of skeletal formation. Prostate cancer produces a variety of BMPs, including BMP-6. We tested the hypothesis that BMP-6 contributes to prostate cancer-induced osteosclerosis at bone metastatic sites. Prostate cancer cells and clinical tissues produced BMP-6 that increased with aggressiveness of the tumor. Prostate cancer-conditioned medium induced SMAD phosphorylation in the preosteoblast MC3T3 cells, and phosphorylation was diminished by anti-BMP-6 antibody. Prostate cancer-conditioned medium induced mineralization of MC3T3 cells, which was blocked by both the BMP inhibitor noggin and anti-BMP-6. Human fetal bones were implanted in severe combined immunodeficient mice and after 4 weeks, LuCaP 23.1 prostate cancer cells were injected both s.c. and into the bone implants. Anti-BMP-6 or isotype antibody administration was then initiated. Anti-BMP-6 reduced LuCaP 23.1-induced osteoblastic activity, but had no effect on its osteolytic activity. This was associated with increased osteoblast numbers and osteoblast activity based on bone histomorphometric evaluation. As endothelin-1 has been implicated in bone metastases, we measured serum endothelin-1 levels but found they were not different among the treatment groups. In addition to decreased bone production, anti-BMP-6 reduced intraosseous, but not s.c., tumor size. We found that BMP-2, BMP-4, BMP-6, and BMP-7 had no direct effect on prostate cancer cell growth, but BMP-2 and BMP-6 increased the in vitro invasive ability of prostate cancer cell. These data show that prostate cancer promotes osteoblastic activity through BMP-6 and that, in addition to its bone effects, suggest that BMPs promote the ability of the prostate cancer cells to invade the bone microenvironment. (Cancer Res 2005; 65(18): 8274-85)

show abstract

Section: Discussionmentioning

confidence: 99%

Bone Morphogenetic Protein-6 Promotes Osteoblastic Prostate Cancer Bone Metastases through a Dual Mechanism

et al. 2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…One characteristic of prostate cancer cells is their production of cytokines that favour osteoblastogenesis: ET-1 [30,31], IGF-I and IGF-II, FGF-1 and FGF-2, VEGF. In turn, activated osteoblasts can release large amounts of IL-6, TGF-β and PDGF-BB which are potent growth factors for the tumour cells [32][33][34]. In both osteoblastic and osteoclastic metastases, a vicious circle is established since the malignant cells stimulate osteoblast or osteoclastic activity, which in turn stimulates tumour growth and progression.…”

Section: Bone Metastasismentioning

confidence: 99%

Cancer-associated bone disease

Rizzoli

Body²,

Brandi³

et al. 2013

Osteoporos Int

125

103

View full text Add to dashboard Cite

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancerassociated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidencebased care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organizations. Epidemiology of cancer-associated bone disease Bone metastasisCancer affects nearly 12.7 million people and is associated with over 7 million deaths in 2008 [1]. Cancer is a rising global health burden and it is estimated that in 2030, cancer deaths will be tallied at over 13 million (World Health Organization (WHO) 2010 Global Status Report [2]). Addressing the morbidity and mortality of cancer is an important public health concern. On purpose, we are limiting our analysis to cancer bone involvement in adults and do not discuss cancer in children.Metastases from cancer are associated with 90 % of cancer deaths [3]. It was estimated that one half of people who die from cancer in the USA have bone involvement [4][5][6]. Different tumou...

show abstract

“…BDSC-2 were obtained from the 11th rib of a 58-year-old man during left nephroureterectomy for localized ureteral cancer. These bone samples were cut into bone chips and further processed with a bone grinder (Lu et al 2004). Bone chips were then cultured in RPMI-10% FCS like prostate-derived stromal cells.…”

Section: Isolation Of Stromal Cells From Prostate Carcinoma Tissuementioning

confidence: 99%

Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of testosterone and dihydrotestosterone from dehydroepiandrosterone

Mizokami

Koh

Izumi

et al. 2009

Endocrine-Related Cancer

Self Cite

View full text Add to dashboard Cite

One of the mechanisms through which advanced prostate cancer (PCa) usually relapses after androgen deprivation therapy (ADT) is the adaptation to residual androgens in PCa tissue. It has been observed that androgen biosynthesis in PCa tissue plays an important role in this adaptation. In the present study, we investigated how stromal cells affect adrenal androgen dehydroepiandrosterone (DHEA) metabolism in androgen-sensitive PCa LNCaP cells. DHEA alone had little effect on prostate-specific antigen (PSA) promoter activity and the proliferation of LNCaP cells. However, the addition of prostate stromal cells or PCa-derived stromal cells (PCaSC) increased DHEA-induced PSA promoter activity via androgen receptor activation in the LNCaP cells. Moreover, PCaSC stimulated the proliferation of LNCaP cells under physiological concentrations of DHEA. Biosynthesis of testosterone or dihydrotestosterone from DHEA in stromal cells and LNCaP cells was involved in this stimulation of LNCaP cell proliferation. Androgen biosynthesis from DHEA depended upon the activity of various steroidogenic enzymes present in stromal cells. Finally, the dual 5a-reductase inhibitor dutasteride appears to function not only as a 5a-reductase inhibitor but also as a 3b-hydroxysteroid dehydrogenase inhibitor in LNCaP cells. Taken together, this coculture assay system provides new insights of coordinate androgen biosynthesis under the microenvironment of PCa cells before and after ADT, and offers a model system for the identification of important steroidogenic enzymes involved in PCa progression and for the development of the corresponding inhibitors of androgen biosynthesis.

show abstract

Osteoblasts induce prostate cancer proliferation and PSA expression through interleukin-6-mediated activation of the androgen receptor

Cited by 56 publications

References 42 publications

Bone Morphogenetic Protein-6 Promotes Osteoblastic Prostate Cancer Bone Metastases through a Dual Mechanism

Bone Morphogenetic Protein-6 Promotes Osteoblastic Prostate Cancer Bone Metastases through a Dual Mechanism

Cancer-associated bone disease

Prostate cancer stromal cells and LNCaP cells coordinately activate the androgen receptor through synthesis of testosterone and dihydrotestosterone from dehydroepiandrosterone

Contact Info

Product

Resources

About