Functional significance of secreted frizzled-related protein 1 in metastatic renal cell carcinomas

Sharanjot Saini, Jan Liu, Soichiro Yamamura, Shahana Majid, Kazumori Kawakami, Hiroshi Hirata, Rajvir Dahiya

Research output: Contribution to journalArticle

Abstract

The secreted Frizzled-related protein 1 (SFRP1) is a Wingless-type (Wnt) antagonist that has been associated with various malignancies, including renal cell carcinomas (RCC). However, the functional significance of SFRP1 has never been investigated in metastatic RCC. Here, we investigated the role of this molecule in kidney cancer progression and metastasis. Using Wnt pathway-focused cDNA expression profiling in normal renal, primary RCC, and metastatic RCC cell lines, we identified that SFRP1 is up-regulated in metastatic RCC. SFRP1 overexpression in metastatic RCC was confirmed by immunostaining in renal tissues. We explored the molecular mechanisms underlying SFRP1 up-regulation by analyzing DNA methylation and histone modification patterns on SFRP1 promoter. We found that this gene is unmethylated/hypomethylated and enriched in activating histone modifications in metastatic RCC. To understand the functional significance of SFRP1 overexpression in metastatic RCC with regard to tumorigenesis, we used a small interfering RNA-mediated approach to knockdown the gene and monitored cellular proliferation, apoptosis, and metastatic behavior. Proliferation was unaltered and apoptosis increased on attenuation of SFRP1 expression. Also, SFRP1 depletion decreased the invasive potential of the metastatic RCC cell line, suggesting that the overexpression of this Wnt antagonist may be related to invasiveness and metastatic behavior in RCC. We investigated the molecular basis of the role of SFRP1 in invasion and metastasis and found that matrix metalloproteinase MMP10 is regulated by SFRP1. In conclusion, our data suggest that SFRP1 plays a role in the metastatic potential of RCC. The present findings may be important in the design of treatment modalities for metastatic RCC.

Original languageEnglish (US)
Pages (from-to)6815-6822
Number of pages8
JournalCancer Research
Volume69
Issue number17
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Fingerprint

Renal Cell Carcinoma
Histone Code
frizzled related protein-1
Apoptosis
Neoplasm Metastasis
Gene Knockdown Techniques
Kidney
Cell Line
Kidney Neoplasms
DNA Methylation
Matrix Metalloproteinases
Small Interfering RNA
Carcinogenesis
Up-Regulation
Complementary DNA
Cell Proliferation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Saini, S., Liu, J., Yamamura, S., Majid, S., Kawakami, K., Hirata, H., & Dahiya, R. (2009). Functional significance of secreted frizzled-related protein 1 in metastatic renal cell carcinomas. Cancer Research, 69(17), 6815-6822. https://doi.org/10.1158/0008-5472.CAN-09-1254

Functional significance of secreted frizzled-related protein 1 in metastatic renal cell carcinomas. / Saini, Sharanjot; Liu, Jan; Yamamura, Soichiro; Majid, Shahana; Kawakami, Kazumori; Hirata, Hiroshi; Dahiya, Rajvir.

In: Cancer Research, Vol. 69, No. 17, 01.09.2009, p. 6815-6822.

Research output: Contribution to journalArticle

Saini, S, Liu, J, Yamamura, S, Majid, S, Kawakami, K, Hirata, H & Dahiya, R 2009, 'Functional significance of secreted frizzled-related protein 1 in metastatic renal cell carcinomas', Cancer Research, vol. 69, no. 17, pp. 6815-6822. https://doi.org/10.1158/0008-5472.CAN-09-1254
Saini, Sharanjot ; Liu, Jan ; Yamamura, Soichiro ; Majid, Shahana ; Kawakami, Kazumori ; Hirata, Hiroshi ; Dahiya, Rajvir. / Functional significance of secreted frizzled-related protein 1 in metastatic renal cell carcinomas. In: Cancer Research. 2009 ; Vol. 69, No. 17. pp. 6815-6822.
@article{c4325a92c323475abac8f848e2eacefe,
title = "Functional significance of secreted frizzled-related protein 1 in metastatic renal cell carcinomas",
abstract = "The secreted Frizzled-related protein 1 (SFRP1) is a Wingless-type (Wnt) antagonist that has been associated with various malignancies, including renal cell carcinomas (RCC). However, the functional significance of SFRP1 has never been investigated in metastatic RCC. Here, we investigated the role of this molecule in kidney cancer progression and metastasis. Using Wnt pathway-focused cDNA expression profiling in normal renal, primary RCC, and metastatic RCC cell lines, we identified that SFRP1 is up-regulated in metastatic RCC. SFRP1 overexpression in metastatic RCC was confirmed by immunostaining in renal tissues. We explored the molecular mechanisms underlying SFRP1 up-regulation by analyzing DNA methylation and histone modification patterns on SFRP1 promoter. We found that this gene is unmethylated/hypomethylated and enriched in activating histone modifications in metastatic RCC. To understand the functional significance of SFRP1 overexpression in metastatic RCC with regard to tumorigenesis, we used a small interfering RNA-mediated approach to knockdown the gene and monitored cellular proliferation, apoptosis, and metastatic behavior. Proliferation was unaltered and apoptosis increased on attenuation of SFRP1 expression. Also, SFRP1 depletion decreased the invasive potential of the metastatic RCC cell line, suggesting that the overexpression of this Wnt antagonist may be related to invasiveness and metastatic behavior in RCC. We investigated the molecular basis of the role of SFRP1 in invasion and metastasis and found that matrix metalloproteinase MMP10 is regulated by SFRP1. In conclusion, our data suggest that SFRP1 plays a role in the metastatic potential of RCC. The present findings may be important in the design of treatment modalities for metastatic RCC.",
author = "Sharanjot Saini and Jan Liu and Soichiro Yamamura and Shahana Majid and Kazumori Kawakami and Hiroshi Hirata and Rajvir Dahiya",
year = "2009",
month = "9",
day = "1",
doi = "10.1158/0008-5472.CAN-09-1254",
language = "English (US)",
volume = "69",
pages = "6815--6822",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "17",

}

TY - JOUR

T1 - Functional significance of secreted frizzled-related protein 1 in metastatic renal cell carcinomas

AU - Saini, Sharanjot

AU - Liu, Jan

AU - Yamamura, Soichiro

AU - Majid, Shahana

AU - Kawakami, Kazumori

AU - Hirata, Hiroshi

AU - Dahiya, Rajvir

PY - 2009/9/1

Y1 - 2009/9/1

N2 - The secreted Frizzled-related protein 1 (SFRP1) is a Wingless-type (Wnt) antagonist that has been associated with various malignancies, including renal cell carcinomas (RCC). However, the functional significance of SFRP1 has never been investigated in metastatic RCC. Here, we investigated the role of this molecule in kidney cancer progression and metastasis. Using Wnt pathway-focused cDNA expression profiling in normal renal, primary RCC, and metastatic RCC cell lines, we identified that SFRP1 is up-regulated in metastatic RCC. SFRP1 overexpression in metastatic RCC was confirmed by immunostaining in renal tissues. We explored the molecular mechanisms underlying SFRP1 up-regulation by analyzing DNA methylation and histone modification patterns on SFRP1 promoter. We found that this gene is unmethylated/hypomethylated and enriched in activating histone modifications in metastatic RCC. To understand the functional significance of SFRP1 overexpression in metastatic RCC with regard to tumorigenesis, we used a small interfering RNA-mediated approach to knockdown the gene and monitored cellular proliferation, apoptosis, and metastatic behavior. Proliferation was unaltered and apoptosis increased on attenuation of SFRP1 expression. Also, SFRP1 depletion decreased the invasive potential of the metastatic RCC cell line, suggesting that the overexpression of this Wnt antagonist may be related to invasiveness and metastatic behavior in RCC. We investigated the molecular basis of the role of SFRP1 in invasion and metastasis and found that matrix metalloproteinase MMP10 is regulated by SFRP1. In conclusion, our data suggest that SFRP1 plays a role in the metastatic potential of RCC. The present findings may be important in the design of treatment modalities for metastatic RCC.

AB - The secreted Frizzled-related protein 1 (SFRP1) is a Wingless-type (Wnt) antagonist that has been associated with various malignancies, including renal cell carcinomas (RCC). However, the functional significance of SFRP1 has never been investigated in metastatic RCC. Here, we investigated the role of this molecule in kidney cancer progression and metastasis. Using Wnt pathway-focused cDNA expression profiling in normal renal, primary RCC, and metastatic RCC cell lines, we identified that SFRP1 is up-regulated in metastatic RCC. SFRP1 overexpression in metastatic RCC was confirmed by immunostaining in renal tissues. We explored the molecular mechanisms underlying SFRP1 up-regulation by analyzing DNA methylation and histone modification patterns on SFRP1 promoter. We found that this gene is unmethylated/hypomethylated and enriched in activating histone modifications in metastatic RCC. To understand the functional significance of SFRP1 overexpression in metastatic RCC with regard to tumorigenesis, we used a small interfering RNA-mediated approach to knockdown the gene and monitored cellular proliferation, apoptosis, and metastatic behavior. Proliferation was unaltered and apoptosis increased on attenuation of SFRP1 expression. Also, SFRP1 depletion decreased the invasive potential of the metastatic RCC cell line, suggesting that the overexpression of this Wnt antagonist may be related to invasiveness and metastatic behavior in RCC. We investigated the molecular basis of the role of SFRP1 in invasion and metastasis and found that matrix metalloproteinase MMP10 is regulated by SFRP1. In conclusion, our data suggest that SFRP1 plays a role in the metastatic potential of RCC. The present findings may be important in the design of treatment modalities for metastatic RCC.

UR - http://www.scopus.com/inward/record.url?scp=70149122998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70149122998&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-09-1254

DO - 10.1158/0008-5472.CAN-09-1254

M3 - Article

C2 - 19723665

AN - SCOPUS:70149122998

VL - 69

SP - 6815

EP - 6822

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 17

ER -