Cancer and Bone*

Guise, Theresa A.; Mundy, Gregory R.

doi:10.1210/edrv.19.1.0323

Cited by 254 publications

(258 citation statements)

References 373 publications

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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%

“…16,17 Recent studies have established that bone resorption by osteoclasts is an important step in the process of bone invasion and metastasis in several malignancies. 18 Various cytokines such as IL-1a, IL-6, tumor necrosis factor (TNF)a and PTH-related protein (PTHrP) released from tumor cells have been shown to activate osteoclastic bone resorption. 18 The RANKL/RANK signaling pathway regulates bone invasion or bone metastasis by several types of human cancer, such as breast cancer, 19,20 prostate cancer, 21,22 myeloma 23,24 and oral SCC.…”

mentioning

confidence: 99%

“…18 Various cytokines such as IL-1a, IL-6, tumor necrosis factor (TNF)a and PTH-related protein (PTHrP) released from tumor cells have been shown to activate osteoclastic bone resorption. 18 The RANKL/RANK signaling pathway regulates bone invasion or bone metastasis by several types of human cancer, such as breast cancer, 19,20 prostate cancer, 21,22 myeloma 23,24 and oral SCC. 25 Interesting and controversial new questions have arisen concerning the direct expression and production of RANKL by human cancer cells: Some evidence suggests that RANKL/OPG expression ratio in osteoblasts/stromal cells is the critical factor regulating osteoclastogenesis under both physiological and pathological conditions.…”

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confidence: 99%

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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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Section: Cell Linesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…In particular urokinase plasminogen activator and uPA-R may contribute to the development of an active crosstalk between tumor cells and host cells. This aspect has suggested the hypothesis of a vicious circle, according to which the establishment and growth of metastatic PCa in bone is determined by an overlapping cellular loop between tumor cells and bone cells (Guise & Mundy 1998). uPA-R is the best known modulator of uPA activation and it is expressed both by invasive PCa cells and normal osteoblasts (Rabbani et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Suppression of EGF-R signaling reduces the incidence of prostate cancer metastasis in nude mice

Angelucci¹,

Gravina²,

Rucci³

et al. 2006

Endocr Relat Cancer

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The activation of epidermal growth factor receptor (EGF-R) plays a key role in the promotion of proliferation and invasion in prostatic carcinoma (PCa). Gefitinib (Iressa; ZD1839), an orally active EGF-R tyrosine kinase inhibitor, has shown an important anti-proliferative activity in tumors expressing EGF-R both in vitro and in vivo. Our aim was to elucidate the role of gefitinib in the modulation of the metastatic spread of PCa cells. The therapeutic role of gefitinib was investigated by evaluating the proliferative and invasive ability of the PCa cell line PC3 and of its high metastatic sub-line, PCb2, by in vitro assays and intracardiac injection in nude mice. The inhibitory effect of gefitinib was tested in vivo by injecting PCa cells subcutaneously or in the left ventricle of nude mice and by administrating daily 150 mg/kg of gefitinib. While xenograft growth was equally reduced in all PCa lines (about 50%), the bone metastasis formation was inhibited especially for the high metastatic PCb2 sub-line (81%) in comparison to PC3 cells (47%). The comparative in vitro analysis among PCa cell lines showed that PCb2 cells were more sensitive to the inhibitory effect of gefitinib in their invasive ability compared to parental PC3 cells but not in their proliferation rate. Moreover, PCb2 cells demonstrated an increased invasive ability in vitro in response to bone stromal cell conditioned medium (BCM). The simultaneous presence of 0.1 ng/ml gefitinib was sufficient to reduce the number of invaded cells in the presence of both EGF and BCM. The molecular characterization of the highly aggressive PCa sub-lines demonstrated that this phenomenon was associated with an increment in uPA/uPAR axis but not in EGF-R expression. In conclusion, our data suggest that the use of gefitinib as a therapeutic agent may be indicated in the control of PCa spreading to bone.

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“…Furthermore, lifethreatening hypercalcemia can develop in patients with metastatic bone disease as a result of excessive bone resorption. (1,3) Thus, prevention and rational management of this pathological condition would benefit many patients suffering from breast cancer. For this aim, it is necessary to understand the mechanisms of bone destruction by metastatic tumors.…”

mentioning

confidence: 99%

Involvement of Cyclo-Oxygenase-2 in Osteoclast Formation and Bone Destruction in Bone Metastasis of Mammary Carcinoma Cell Lines

Ono

Akatsu

Murakami

et al. 2002

Journal of Bone and Mineral Research

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Cancer and Bone*

Cited by 254 publications

References 373 publications

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

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

Suppression of EGF-R signaling reduces the incidence of prostate cancer metastasis in nude mice

Involvement of Cyclo-Oxygenase-2 in Osteoclast Formation and Bone Destruction in Bone Metastasis of Mammary Carcinoma Cell Lines

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