Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma

Kyung Kim Hee, Hong Zhang, Hui Li, Tsung Teh Wu, Stephen Swisher, Donggou He, Lizhi Wu, Jianmin Xu, Craig A. Elmets, Mohammad Athar, Xìao Chun Xu, Hui Xu

Research output: Contribution to journalArticle

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Abstract

Slits are a group of secreted glycoproteins that play a role in the regulation of cell migration. Previous studies suggested that Slit2 might be a tumor-suppressor gene. However, it remained to be determined whether Slit2 suppressed tumor growth and metastasis in animal models. We showed that Slit2 expression was decreased or abolished in human esophageal squamous cell carcinomas (SCCs) compared to normal tissues by in situ hybridization. Stable transfection of human SCC A431 and fibrosarcoma HT1080 cells with Slit2 gene suppressed tumor growth in athymic nude mice. Apoptosis in Slit2-transfected tumors was increased, whereas proliferating cells were decreased, suggesting a mechanism for Slit2-mediated tumor suppression. This was supported by further analysis indicating that antiapoptotic molecules Bcl-2 and Bcl-xl and cell cycle molecules Cdk6 and Cyclin D1 were downregulated in Slit2-transfected tumors. Furthermore, wound healing and Matrigel invasion assays showed that the transfection with Slit2 inhibited tumor cell migration and invasion. Slit2-transfected tumors showed a high level of keratin 8/18 and a low level of N-cadherin expression compared to empty vector-transfected tumors. More importantly, Slit2 transfection suppressed the metastasis of HT1080 tumor cells in lungs after intravenous inoculation. Collectively, our study has demonstrated that Slit2 inhibits tumor growth and metastasis of fibrosarcoma and SCC and that its effect on cell cycle and apoptosis signal pathways is an important mechanism for Slit2-mediated tumor suppression.

Original languageEnglish (US)
Pages (from-to)1411-1420
Number of pages10
JournalNeoplasia
Volume10
Issue number12
DOIs
StatePublished - Dec 2008
Externally publishedYes

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Fibrosarcoma
Squamous Cell Carcinoma
Neoplasm Metastasis
Growth
Neoplasms
Transfection
Nude Mice
Cell Movement
Cell Cycle
Keratin-8
Apoptosis
Keratin-18
Cyclin D1
Cadherins
Tumor Suppressor Genes
Wound Healing
In Situ Hybridization
Signal Transduction
Glycoproteins
Down-Regulation

ASJC Scopus subject areas

  • Cancer Research

Cite this

Hee, K. K., Zhang, H., Li, H., Wu, T. T., Swisher, S., He, D., ... Xu, H. (2008). Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma. Neoplasia, 10(12), 1411-1420. https://doi.org/10.1593/neo.08804

Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma. / Hee, Kyung Kim; Zhang, Hong; Li, Hui; Wu, Tsung Teh; Swisher, Stephen; He, Donggou; Wu, Lizhi; Xu, Jianmin; Elmets, Craig A.; Athar, Mohammad; Xu, Xìao Chun; Xu, Hui.

In: Neoplasia, Vol. 10, No. 12, 12.2008, p. 1411-1420.

Research output: Contribution to journalArticle

Hee, KK, Zhang, H, Li, H, Wu, TT, Swisher, S, He, D, Wu, L, Xu, J, Elmets, CA, Athar, M, Xu, XC & Xu, H 2008, 'Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma', Neoplasia, vol. 10, no. 12, pp. 1411-1420. https://doi.org/10.1593/neo.08804
Hee KK, Zhang H, Li H, Wu TT, Swisher S, He D et al. Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma. Neoplasia. 2008 Dec;10(12):1411-1420. https://doi.org/10.1593/neo.08804
Hee, Kyung Kim ; Zhang, Hong ; Li, Hui ; Wu, Tsung Teh ; Swisher, Stephen ; He, Donggou ; Wu, Lizhi ; Xu, Jianmin ; Elmets, Craig A. ; Athar, Mohammad ; Xu, Xìao Chun ; Xu, Hui. / Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma. In: Neoplasia. 2008 ; Vol. 10, No. 12. pp. 1411-1420.
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