Osteoprotegerin and rank ligand expression in prostate cancer

Brown, Johnny E.; Corey, Eva; Lee, Zandra D; True, Lawrence D.; Yun, Theodore J.; Tondravi, Mehrdad; Vessella, Robert L.

doi:10.1016/s0090-4295(00)01122-5

Cited by 209 publications

(157 citation statements)

References 16 publications

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“…Our data clearly indicate that expression of RANKL is not uniform throughout the epidermis, but that maximal levels are present in the suprabasal compartment, precisely where LC reside. This echoes observations made in prostate epithelium where RANKL expression was found increased in luminal cells compared with basal cells (27). The mechanism underlying this regulated expression is unidentified.…”

Section: Discussionsupporting

confidence: 85%

Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

Barbaroux

Beleut

Brisken

et al. 2008

The Journal of Immunology

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Langerhans cells (LC) are the dendritic APC population of the epidermis, where they reside for long periods and are self-replicating. The molecular signals underlying these characteristics are unknown. The TNF superfamily member receptor activator of NF-κB ligand (RANKL, TNFSF11) has been shown to sustain viability of blood dendritic cells in addition to its role in promoting proliferation and differentiation of several cell types, notably osteoclasts. In this study, we have studied expression of the RANKL system in skin and have defined a key role for this molecule in LC homeostasis. In vitro and in vivo, human KC expressed RANKL and epidermal LC expressed cell surface RANK. In vitro, RANKL sustained CD34+ progenitor-derived LC viability following 72-h cultures in cytokine-free medium (79.5 ± 1% vs 55.2 ± 5.7% live cells, respectively; n = 4; p < 0.05). In vivo, RANKL-deficient mice displayed a marked reduction in epidermal LC density (507.1 ± 77.2 vs 873.6 ± 41.6 LC per mm2; n = 9; p < 0.05) and their proliferation was impaired without a detectable effect on apoptosis. These data indicate a key role for the RANKL system in the regulation of LC survival within the skin and suggest a regulatory role for KC in the maintenance of epidermal LC homeostasis.

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Section: Discussionsupporting

confidence: 85%

Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

Barbaroux

Beleut

Brisken

et al. 2008

The Journal of Immunology

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“…RANKL is highly expressed and involved in the tumorigenesis and metastasis of multiple myelomas (Sezer et al, 2002), giant cell tumors of the bone (Roux et al, 2002), prostate cancers (Brown et al, 2001), and neuroblastomas (Michigami et al, 2001). We show that RANKL is overexpressed in most constitutive mutants, and in colon cancer RKO, cervix cancer Hela, and prostate cancer DU145 cells.…”

Section: Discussionmentioning

confidence: 99%

Secretion of cytokines and growth factors as a general cause of constitutive NFκB activation in cancer

et al. 2003

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The constitutive activation of nuclear factor jB (NFjB) helps a variety of tumors to resist apoptosis and desensitizes them to chemotherapy, but the causes are still largely unknown. We have analysed this phenomenon in eight mutant cell lines derived from human 293 cells, selected for NFjB-dependent expression of a marker gene, and also in seven tumor-derived cell lines. Conditioned media from all of these cells stimulated the activation of NFjB (up to 30-fold) in indicator cells carrying an NFjB-responsive reporter. Therefore, secretion of extracellular factors as the cause of constitutive activation seems to be general. The mRNAs encoding several different cytokines and growth factors were greatly overexpressed in the tumor and mutant cells. The pattern of overexpression was distinct in each cell line, indicating that the phenomenon is complex. Two secreted factors whose roles in the constitutive activation of NFjB are not well defined were investigated further as pure proteins: transforming growth factor b2 (TGFb2) and fibroblast growth factor 5 (FGF5) were both highly expressed in some mutant clones and tumor cell lines, each activated NFjB alone, and the combination was synergistic. Our data indicate that a group of different factors, expressed at abnormally high levels, can contribute singly and synergistically to the constitutive activation of NFjB in all of the mutant and tumor cell lines we studied. Since several NFjB target genes encode secreted proteins that induce NFjB, autocrine loops are likely to be ubiquitously important in the constitutive activation of NFjB in cancer. We provide the first evidence of the general, complex, and synergistic activation of NFjB in tumor and mutant cell lines through the action of secreted factors and suggest that the same explanation is likely for the constitutive activation of NFjB in cancers.

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“…Other oral SCC cell lines used in our study were HSC-2 and Ca [9][10][11][12][13][14][15][16][17][18][19][20][21][22] , purchased from the Japanese Cancer Research Resource Bank-Cell (JCRB) (Tokyo, Japan). The cells were maintained in Dulbecco's Modified Eagle's Medium (DMEM) containing 10% fetal bovine serum (FBS).…”

Section: Cell Linesmentioning

confidence: 99%

Oral squamous cell carcinoma cells induce osteoclast differentiation by suppression of osteoprotegerin expression in osteoblasts

Tada

Jimi

Okamoto

et al. 2005

Intl Journal of Cancer

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The invasion of oral squamous cell carcinoma (SCC) cells into the mandibular bone is a common clinical problem. It has been reported that BHY cells, a human oral SCC cell line, are capable of invading mandibular bone of nude mice. These results led us to examine possible mechanisms of osteoclastogenesis induced by BHY cells using in vitro culture systems. When BHY cells were cocultured with mouse bone marrow cells (BMCs), only few osteoclasts were formed, even though BHY cells express the receptor activator of NF-jB ligand (RANKL). However, adding BHY cells to a coculture of mouse primary osteoblasts (POBs) and BMCs markedly induced osteoclastogenesis in the absence of osteotropic factors. Furthermore, another oral SCC cell line, HSC-2, which does not express RANKL, also induced osteoclastogenesis in our cocultures. These effects were significantly, but not completely, inhibited by adding osteoprotegerin (OPG). In addition, we also found that TNFa released from these cells partially contributes to osteoclastogenesis via a RANKL-independent mechanism. Adding BHY or HSC-2 cells suppressed mouse OPG mRNA expression and protein production by POBs in cocultures of POBs and human oral SCC cells. This finding is consistent with the result that BHY cells and HSC-2 cells did not enhance osteoclastogenesis in cocultures of BMCs and POBs from OPG-deficient mice. Immunohistochemical analysis showed a reduction of OPG expression in osteolytic lesions as compared to normal lesions from oral SCC patients. Therefore, oral SCC-induced suppression of OPG expression in POBs appears critical for osteoclastogenesis, rather than expression of RANKL in SCC cells. ' 2005 Wiley-Liss, Inc.Key words: squamous cell carcinoma; RANKL; OPG; osteoclastogenesis Oral cancer most commonly involves the tissue of the tongue and the lips, and it can also occur on the floor of the mouth, gingiva or plate.1,2 The vast majority of oral cancers are squamous cell carcinomas (SCCs) 1,2 and oral SCCs frequently invade the mandibular bone. Advanced oral SCC has a high mortality and treatment is complicated by the disruption of speech and swallowing after surgical resection. It is generally agreed that patients with mandibular invasion should be treated surgically, but the extent of mandibular resection required remains controversial. Resection of the mandibular bone leads to physical damage as well as frequent psychological problems for the patients.It is well known that oral SCC invades the mandibular bone by direct extension and not by metastasis.3,4 Previous studies have suggested that the bone destruction associated with carcinoma invasion is mediated by osteoclasts rather than directly by the carcinoma.3,4 Invasion of the mandible by oral SCC is currently established only by radiological inspection. The cellular and molecular mechanisms regulating bone invasion and osteoclastic bone resorption by oral SCC are poorly understood.Osteoclasts are multinucleated cells that are responsible for bone resorption. [5][6][7] Osteoclastic bone resorption consists...

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Osteoprotegerin and rank ligand expression in prostate cancer

Cited by 209 publications

References 16 publications

Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

Secretion of cytokines and growth factors as a general cause of constitutive NFκB activation in cancer

Oral squamous cell carcinoma cells induce osteoclast differentiation by suppression of osteoprotegerin expression in osteoblasts

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