Secreted frizzled related protein (sFRP)-2 inhibits bone formation and promotes cell proliferation in ameloblastoma

Sathi, Gulsan Ara; Inoue, Miho; Harada, Hidemitsu; Rodrı́guez, Augusto; Tamamura, Ryo; Tsujigiwa, Hidetsugu; Borkosky, Silvia Susana; Gündüz, Mehmet; Nagatsuka, Hitoshi

doi:10.1016/j.oraloncology.2009.02.001

Cited by 28 publications

(17 citation statements)

References 24 publications

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“…Interestingly, we found reduced bone expression of the Wnt inhibitors Dkk3, Sost, Sfrp2 and Sfrp3 in Sfrp4 -/-mice. These Wnt antagonists suppress osteoblast formation and bone growth (21)(22)(23)(24)(25)(26)(27). However, only mice deficient in Sost and Sfrp3 have increased bone mass (28 -32).…”

Section: Discussionmentioning

confidence: 99%

Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice

et al. 2015

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Secreted frizzled-related protein 4 (SFRP4) is an extracellular regulator of the wingless-type mouse mammary tumor virus integration site family (WNT) pathway. SFRP4 has been implicated in adipocyte dysfunction, obesity, insulin resistance, and impaired insulin secretion in patients with type 2 diabetes. However, the exact role of SFRP4 in regulating whole-body metabolism and glucose homeostasis is unknown. We show here that male Sfrp4(-/-) mice have increased spine length and gain more weight when fed a high-fat diet. The body composition and body mass per spine length of diet-induced obese Sfrp4(-/-) mice is similar to wild-type littermates, suggesting that the increase in body weight can be accounted for by their longer body size. The diet-induced obese Sfrp4(-/-) mice have reduced energy expenditure, food intake, and bone mineral density. Sfrp4(-/-) mice have normal glucose and insulin tolerance and β-cell mass. Diet-induced obese Sfrp4(-/-) and control mice show similar impairments of glucose tolerance and a 5-fold compensatory expansion of their β-cell mass. In summary, our data suggest that loss of SFRP4 alters body length and bone mineral density as well as energy expenditure and food intake. However, SFRP4 does not control glucose homeostasis and β-cell mass in mice.

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Section: Discussionmentioning

confidence: 99%

Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice

et al. 2015

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“…Research has demonstrated that the inhibition of fibroblast apoptosis and proliferation promotion are key processes in the formation of HS [1]; [5]. The proliferation level of HSFBs was higher than that of normal skin fibroblasts, and some studies have shown that SFRP2 may also directly modulate cell proliferation in other diseases [24]. Our previous study [13], however, failed to observe that SFRP2 shRNA had a significant suppression effects on the proliferation of HSFBs, suggesting that SFRP2 was not associated with the proliferation of HSFBs.…”

Section: Discussionmentioning

confidence: 99%

SFRP2 and Slug Contribute to Cellular Resistance to Apoptosis in Hypertrophic Scars

et al. 2012

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Hypertrophic scars (HS) are skin disorders which occur after wounding and thermal injury. Our previous studies have suggested that secreted frizzled-related protein 2 (SFRP2) is involved in HS formation and that the suppression of SFRP2 promotes apoptosis of hypertrophic scar fibroblasts (HSFBs). However, the mechanisms have not been clarified. Previous studies revealed that Slug expression inhibits cell apoptosis, in vitro and in vivo, and SFRP2 regulates the expression of Slug in cervical cancer cells. In the present study, we quantified differential expression levels of expression of SFRP2 and Slug in HS and normal skin tissues by immunohistochemistry, both of which have important anti-apoptosis roles. Furthermore, a short hairpin RNA approach was adopted to investigate the potential function of SFRP2 and Slug in HSFB apoptosis. Cell apoptosis was detected using fluorescence-activated cell sorting and Caspase-3 activity was assayed by spectrophotometry. This study demonstrates that SFRP2 expression, as well as Slug, is dramatically up-regulated in HS relative to normal skin tissues, and the Slug expression is positively correlated with SFRP2. Slug expression was down-regulated in SFRP2-deficient cells, and the down-regulation of Slug expression increased sensitivity to apoptosis which was induced through a caspase-3-dependent pathway. The infected cells with reduced levels of Slug were tested for the expression of apoptosis-related genes (Bcl-2, Bax and PUMA) which were previously identified as Slug targets. Bcl-2 expression was down-regulated in Slug-deficient cells. In conclusion, SFRP2 appears to interact with Slug to affect the apoptosis of hypertrophic scar fibroblasts.

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“…Novel strategies for successful tumor treatment should focus on the elimination of CSCs. In this study, we analyzed immunohistochemical staining to detect the expression of three different CSC markers in relation to the proliferation activity of the tumor cells in ameloblastoma, a highly apoptosis-resistant and invasive tumor with a high recurrence rate and possesing different histological patterns (18)(19)(20)(21). Increasing evidence highlights the role of CD133 as a marker of CSCs in various human tumors as well as in ameloblastoma (22,23).…”

Section: Discussionmentioning

confidence: 99%

Analysis of immunoexpression of common cancer stem cell markers in ameloblastoma

Sathi

Tamamura

Tsujigiwa

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Recent studies have established that, in benign tumors, a large number of cancer stem cells are present, which have great implications in tumor development. However, in ameloblastoma, a highly aggressive, locally invasive tumor with a high recurrence rate, whether or not cancer stem-like cells are present remains undetermined. Therefore, in this study we analyzed the protein expression of three candidate stem cell markers in ameloblastoma. Immunohistochemical staining for cancer stem cell (CSC) markers (CD133, CD44 and ABCG2) and for the proliferation marker Ki-67 was performed using 23 ameloblastoma cases. In all 23 samples, CD133, CD44 and ABCG2 were expressed. Nine (39.13%) cases showed high expression and 14 cases (60.87%) showed low expression for CD133. Twelve of the 23 cases (52.17%) showed high expression and 11 cases (47.83%) showed low expression for both CD44 and ABCG2, respectively. Ki-67 was mainly expressed in peripheral ameloblast-like cells, suggesting that these cells have a higher degree of differentiation and, therefore, are less likely to contain cancer stem-like cells. On the other hand, cells positive for CSC markers situated at the close proximity to peripheral cells were devoid of Ki-67 and may have the potential to be cancer stem-like cells. After analyzing the correlation between expression of three CSC markers with clinicopathological factors and Ki-67 expression, only CD44 expression was correlated with tumor recurrence (P=0.0391). In conclusion, this study showed various expression patterns of different types of cancer stem cell markers and the presence of candidate CSC-like cells in ameloblastoma, which are possibly involved in cell proliferation, tumor progression and recurrence.

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Secreted frizzled related protein (sFRP)-2 inhibits bone formation and promotes cell proliferation in ameloblastoma

Cited by 28 publications

References 24 publications

Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice

Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice

SFRP2 and Slug Contribute to Cellular Resistance to Apoptosis in Hypertrophic Scars

Analysis of immunoexpression of common cancer stem cell markers in ameloblastoma

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