Role of secreted frizzled-related protein 3 in human renal cell carcinoma

Hiroshi Hirata, Yuji Hinoda, Koji Ueno, Shahana Majid, Sharanjot Saini, Rajvir Dahiya

Research output: Contribution to journalArticle

Abstract

The secreted frizzled-related protein (sFRP) family plays an important role in the inhibition of the Wnt signaling pathway in various cancers. The functional significance of Wnt antagonist sFRP3 has not been investigated in renal cancer. We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues. Therefore, we hypothesized that sFRP3 may play an important role in metastatic renal cancer. To test this hypothesis, we performed a series of experiments to determine the role of sFRP3 using primary and metastatic renal cancer cell lines. Functional analysis showed increased numbers of viable and invaded cells and tube formation and decreased numbers of apoptotic cells in the sFRP3-transfected renal cancer cell line A498. Promotion of tumor growth was also observed in nude mice injected with sFRP3-transfected A498 cells. In contrast, the number of viable cells and invasive cells was decreased in sFRP3 mRNA knockdown metastatic cells (ACHN and Hs891.T). To investigate the mechanism of sFRP3 function, we performed microarray analysis to see which genes were upregulated or downregulated by sFRP3 expression. Among these genes, MMP-3 and ANGPT1 were significantly upregulated in sFRP3-transfected cells. In conclusion, this is the first report to show that sFRP3 expression promotes cell growth, invasion, and inhibition of apoptosis in renal cancer cells.

Original languageEnglish (US)
Pages (from-to)1896-1905
Number of pages10
JournalCancer Research
Volume70
Issue number5
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Fingerprint

Kidney Neoplasms
Renal Cell Carcinoma
Cell Count
Cell Line
Wnt Signaling Pathway
Microarray Analysis
Growth
Matrix Metalloproteinases
Nude Mice
Genes
frizzled related protein-3
Neoplasms
Down-Regulation
Apoptosis
Kidney
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Role of secreted frizzled-related protein 3 in human renal cell carcinoma. / Hirata, Hiroshi; Hinoda, Yuji; Ueno, Koji; Majid, Shahana; Saini, Sharanjot; Dahiya, Rajvir.

In: Cancer Research, Vol. 70, No. 5, 01.03.2010, p. 1896-1905.

Research output: Contribution to journalArticle

Hirata, H, Hinoda, Y, Ueno, K, Majid, S, Saini, S & Dahiya, R 2010, 'Role of secreted frizzled-related protein 3 in human renal cell carcinoma', Cancer Research, vol. 70, no. 5, pp. 1896-1905. https://doi.org/10.1158/0008-5472.CAN-09-3549
Hirata, Hiroshi ; Hinoda, Yuji ; Ueno, Koji ; Majid, Shahana ; Saini, Sharanjot ; Dahiya, Rajvir. / Role of secreted frizzled-related protein 3 in human renal cell carcinoma. In: Cancer Research. 2010 ; Vol. 70, No. 5. pp. 1896-1905.
@article{adaa585d05cc4821863b118d8d17f173,
title = "Role of secreted frizzled-related protein 3 in human renal cell carcinoma",
abstract = "The secreted frizzled-related protein (sFRP) family plays an important role in the inhibition of the Wnt signaling pathway in various cancers. The functional significance of Wnt antagonist sFRP3 has not been investigated in renal cancer. We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues. Therefore, we hypothesized that sFRP3 may play an important role in metastatic renal cancer. To test this hypothesis, we performed a series of experiments to determine the role of sFRP3 using primary and metastatic renal cancer cell lines. Functional analysis showed increased numbers of viable and invaded cells and tube formation and decreased numbers of apoptotic cells in the sFRP3-transfected renal cancer cell line A498. Promotion of tumor growth was also observed in nude mice injected with sFRP3-transfected A498 cells. In contrast, the number of viable cells and invasive cells was decreased in sFRP3 mRNA knockdown metastatic cells (ACHN and Hs891.T). To investigate the mechanism of sFRP3 function, we performed microarray analysis to see which genes were upregulated or downregulated by sFRP3 expression. Among these genes, MMP-3 and ANGPT1 were significantly upregulated in sFRP3-transfected cells. In conclusion, this is the first report to show that sFRP3 expression promotes cell growth, invasion, and inhibition of apoptosis in renal cancer cells.",
author = "Hiroshi Hirata and Yuji Hinoda and Koji Ueno and Shahana Majid and Sharanjot Saini and Rajvir Dahiya",
year = "2010",
month = "3",
day = "1",
doi = "10.1158/0008-5472.CAN-09-3549",
language = "English (US)",
volume = "70",
pages = "1896--1905",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Role of secreted frizzled-related protein 3 in human renal cell carcinoma

AU - Hirata, Hiroshi

AU - Hinoda, Yuji

AU - Ueno, Koji

AU - Majid, Shahana

AU - Saini, Sharanjot

AU - Dahiya, Rajvir

PY - 2010/3/1

Y1 - 2010/3/1

N2 - The secreted frizzled-related protein (sFRP) family plays an important role in the inhibition of the Wnt signaling pathway in various cancers. The functional significance of Wnt antagonist sFRP3 has not been investigated in renal cancer. We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues. Therefore, we hypothesized that sFRP3 may play an important role in metastatic renal cancer. To test this hypothesis, we performed a series of experiments to determine the role of sFRP3 using primary and metastatic renal cancer cell lines. Functional analysis showed increased numbers of viable and invaded cells and tube formation and decreased numbers of apoptotic cells in the sFRP3-transfected renal cancer cell line A498. Promotion of tumor growth was also observed in nude mice injected with sFRP3-transfected A498 cells. In contrast, the number of viable cells and invasive cells was decreased in sFRP3 mRNA knockdown metastatic cells (ACHN and Hs891.T). To investigate the mechanism of sFRP3 function, we performed microarray analysis to see which genes were upregulated or downregulated by sFRP3 expression. Among these genes, MMP-3 and ANGPT1 were significantly upregulated in sFRP3-transfected cells. In conclusion, this is the first report to show that sFRP3 expression promotes cell growth, invasion, and inhibition of apoptosis in renal cancer cells.

AB - The secreted frizzled-related protein (sFRP) family plays an important role in the inhibition of the Wnt signaling pathway in various cancers. The functional significance of Wnt antagonist sFRP3 has not been investigated in renal cancer. We performed tissue microarray and found that the level of sFRP3 protein was high in normal kidney, low in primary renal cancer tissues, and high in metastatic renal cancer tissues. Therefore, we hypothesized that sFRP3 may play an important role in metastatic renal cancer. To test this hypothesis, we performed a series of experiments to determine the role of sFRP3 using primary and metastatic renal cancer cell lines. Functional analysis showed increased numbers of viable and invaded cells and tube formation and decreased numbers of apoptotic cells in the sFRP3-transfected renal cancer cell line A498. Promotion of tumor growth was also observed in nude mice injected with sFRP3-transfected A498 cells. In contrast, the number of viable cells and invasive cells was decreased in sFRP3 mRNA knockdown metastatic cells (ACHN and Hs891.T). To investigate the mechanism of sFRP3 function, we performed microarray analysis to see which genes were upregulated or downregulated by sFRP3 expression. Among these genes, MMP-3 and ANGPT1 were significantly upregulated in sFRP3-transfected cells. In conclusion, this is the first report to show that sFRP3 expression promotes cell growth, invasion, and inhibition of apoptosis in renal cancer cells.

UR - http://www.scopus.com/inward/record.url?scp=77950190313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950190313&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-09-3549

DO - 10.1158/0008-5472.CAN-09-3549

M3 - Article

C2 - 20160027

AN - SCOPUS:77950190313

VL - 70

SP - 1896

EP - 1905

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 5

ER -