Frzb, a secreted Wnt antagonist, decreases growth and invasiveness of fibrosarcoma cells associated with inhibition of Met signaling

Yi Guo, Jun Xie, Elyssa Rubin, Ya Xiong Tang, Fritz Lin, Xiaolin Zi, Bang H. Hoang

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Soft tissue sarcomas (STS) have a strong propensity for aggressive growth and metastasis. We showed that the secreted Wnt antagonist Frzb exhibited potent antitumor activity against prostate cancer, an epithelial type of malignancy. In this study, we further showed the antitumor efficacy of Frzb in STS, a mesenchymal group of cancer. Frzb transfection of HT1080 (fibrosarcoma) and SW872 (liposarcoma) cell lines and their conditioned media resulted in a significant reduction in cellular invasion, motility, and colony formation in soft agar compared with vector control-transfected cells. In a xenograft mouse model, Frzb dramatically suppressed tumor growth of HT1080 cells in nude mice. In a tail-vein injection metastatic model, Frzb-transfected HT1080 cells formed fewer and smaller lung nodules than vector control cells. In addition, we identified new mechanisms for Frzb antitumor activities. Frzb reduced c-Met expression and inhibited Met-mediated signaling, associated with up-regulation of epithelial markers (i.e., keratins 8 and 18) and down-regulation of mesenchymal markers (i.e., vimentin, N-cadherin, fibronectin, Slug, and Twist). Similar to Frzb, silencing of c-Met by short hairpin RNA or using a dominant-negative LRP5 receptor also suppressed Met signaling, leading to reduced cellular motility, invasion, and in vivo tumor growth. Given recent studies indicating an important role of c-Met in sarcoma development and progression, our data showed that Frzb expression was significantly inversely correlated with Met expression in both STS cell lines and tissues. These results suggested the usefulness of Frzb in modulating Met signaling as a new treatment strategy for STS.

Original languageEnglish (US)
Pages (from-to)3350-3360
Number of pages11
JournalCancer Research
Volume68
Issue number9
DOIs
StatePublished - May 1 2008
Externally publishedYes

Fingerprint

Fibrosarcoma
Sarcoma
Growth
Neoplasms
Keratin-8
Keratin-18
Cell Line
Liposarcoma
Gastropoda
Vimentin
Cadherins
Conditioned Culture Medium
Fibronectins
Heterografts
Nude Mice
Small Interfering RNA
Agar
Transfection
Tail
Veins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Frzb, a secreted Wnt antagonist, decreases growth and invasiveness of fibrosarcoma cells associated with inhibition of Met signaling. / Guo, Yi; Xie, Jun; Rubin, Elyssa; Tang, Ya Xiong; Lin, Fritz; Zi, Xiaolin; Hoang, Bang H.

In: Cancer Research, Vol. 68, No. 9, 01.05.2008, p. 3350-3360.

Research output: Contribution to journalArticle

Guo, Yi ; Xie, Jun ; Rubin, Elyssa ; Tang, Ya Xiong ; Lin, Fritz ; Zi, Xiaolin ; Hoang, Bang H. / Frzb, a secreted Wnt antagonist, decreases growth and invasiveness of fibrosarcoma cells associated with inhibition of Met signaling. In: Cancer Research. 2008 ; Vol. 68, No. 9. pp. 3350-3360.
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