Stable overexpression of Smad7 in human melanoma cells inhibits their tumorigenicity in vitro and in vivo

Javelaud, Delphine; Delmas, Véronique; Møller, Margrethe; Sextius, Peggy; André, Jocelyne; Ménashi, Suzanne; Larue, Lionel; Mauviel, Alain

doi:10.1038/sj.onc.1208900

Cited by 96 publications

(109 citation statements)

References 19 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[10][11][12] It has also been found that TGF-b signaling promotes the anchorage-independent growth and metastatic capability of melanoma cells. 13,14 Consistent with a similar role for Nodal in melanoma aggressiveness, blockade of Nodal signaling in cultured melanoma cells resulted in decreased invasiveness, anchorage-independent growth, and xenograft tumor formation. 15 The initial study of Nodal expression in melanomas supported a role for Nodal signaling in melanomas.…”

mentioning

confidence: 61%

Expression of the embryonic morphogen Nodal in cutaneous melanocytic lesions

Harms

Pouryazdanparast

et al. 2010

Modern Pathology

View full text Add to dashboard Cite

Nodal, a potent embryonic morphogen in the transforming growth factor-b family, is a proposed key regulator of melanoma tumorigenicity. However, there has been no systematic study of Nodal expression in melanocytic lesions. We investigated Nodal expression by immunohistochemistry in 269 melanocytic lesions, including compound nevi, dysplastic nevi, congenital nevi, Spitz nevi, melanoma in situ, malignant melanoma including the variant desmoplastic melanoma, and metastatic melanoma. We found that the Nodal expression was significantly increased in malignant lesions (including melanoma in situ, malignant melanoma, and metastatic melanoma) compared with compound nevi, Spitz nevi, and dysplastic nevi. Surprisingly, congenital nevi expressed a level of Nodal comparable with malignant lesions, whereas desmoplastic melanoma showed lower expression than nondesmoplastic malignant melanoma (Po0.05). Deep melanoma (Breslow depth 41 mm) displayed a higher percentage of Nodal-positive tumor cells than did superficial melanoma (Breslow depth r1 mm), although there was no statistical difference in the overall staining intensity (P ¼ 0.18). Melanomas in situ showed a lower level of Nodal expression than did deep melanomas and metastatic melanomas (Po0.05). The low expression of Nodal in normal and dysplastic nevi, and its increasing expression with the progression of malignant lesions, are suggestive of a role for Nodal in melanoma progression.

show abstract

mentioning

confidence: 61%

Expression of the embryonic morphogen Nodal in cutaneous melanocytic lesions

Harms

Pouryazdanparast

et al. 2010

Modern Pathology

View full text Add to dashboard Cite

show abstract

“…Inhibition of Smad signaling by stable overexpression of Smad7 inhibits the growth of human melanoma xenografts in nude mice, and is associated with reduced MMP production (Javelaud et al, 2005). Furthermore, Smad3 overexpression has prometastatic effects on malignant breast cancer cells (Tian et al, 2003), and a Smadbinding defective mutant of TbRI enhances their tumorigenesis (Tian et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The (CAGA) 9 -Luc construct was used as a reporter construct specific for Smad3/4-driven signaling (28). The pcDNA-Smad7 vector is a kind gift from Dr. Alain Mauviel (19).…”

Section: Transient Cell Transfections Reporter Assays and Plasmid Cmentioning

confidence: 99%

“…Cells were cultured for 48 hours without serum and their conditioned media were analyzed by gelatin zymography in 10% polyacrylamide gels containing 1 mg/mL gelatin (Sigma-Aldrich) as described previously (19).…”

Section: Gelatin Zymographymentioning

confidence: 99%

“…With regard to bone cancers, most studies have focused on the role of TGFb in the development of bone metastasis. The contributions of TGFb to breast cancer and melanoma bone metastasis have been well described (18)(19)(20)(21). TGFb promotes bone metastasis by its ability to promote the metastatic process by stimulating MMP2 production and thus promoting cellular invasion of melanoma (19,20).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Overexpression of Smad7 Blocks Primary Tumor Growth and Lung Metastasis Development in Osteosarcoma

Lamora

Talbot

Bougras

et al. 2014

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Osteosarcoma is the main malignant primary bone tumor in children and adolescents for whom the prognosis remains poor, especially when metastasis is present at diagnosis. Because transforming growth factor-b (TGFb) has been shown to promote metastasis in many solid tumors, we investigated the effect of the natural TGFb/Smad signaling inhibitor Smad7 and the TbRI inhibitor SD-208 on osteosarcoma behavior.Experimental Design: By using a mouse model of osteosarcoma induced by paratibial injection of cells, we assessed the impact of Smad7 overexpression or SD-208 on tumor growth, tumor microenvironment, bone remodeling, and metastasis development.Results: First, we demonstrated that TGFb levels are higher in serum samples from patients with osteosarcoma compared with healthy volunteers and that TGFb/Smad3 signaling pathway is activated in clinical samples. Second, we showed that Smad7 slows the growth of the primary tumor and increases mice survival. We furthermore demonstrated that Smad7 expression does not affect in vitro osteosarcoma cell proliferation but affects the microarchitectural parameters of bone. In addition, Smad7-osteosarcoma bone tumors expressed lower levels of osteolytic factors such as RANKL, suggesting that Smad7 overexpression affects the "vicious cycle" established between tumor cells and bone cells by its ability to decrease osteoclast activity. Finally, we showed that Smad7 overexpression in osteosarcoma cells and the treatment of mice with SD208 inhibit the development of lung metastasis.Conclusion: Taken together, these results demonstrate that the inhibition of the TGFb/Smad signaling pathway may be a promising therapeutic strategy against tumor progression of osteosarcoma, specifically against the development of lung metastasis.

show abstract

Stable overexpression of Smad7 in human melanoma cells inhibits their tumorigenicity in vitro and in vivo

Cited by 96 publications

References 19 publications

Expression of the embryonic morphogen Nodal in cutaneous melanocytic lesions

Expression of the embryonic morphogen Nodal in cutaneous melanocytic lesions

Activation of Smad signaling enhances collagenase-3 (MMP-13) expression and invasion of head and neck squamous carcinoma cells

Overexpression of Smad7 Blocks Primary Tumor Growth and Lung Metastasis Development in Osteosarcoma

Contact Info

Product

Resources

About