BACKGROUND: The SDF-1/CXCR4 axis plays an important role in cancer metastasis. SDF1alpha genetic polymorphisms, including SDF1alpha-G801A, have been associated with increased cancer risk and may be predictive of distant metastasis. The present study compared the frequency of 6 SDF1alpha single-nucleotide polymorphisms (SNPs) in patients with colorectal cancer (CRC) with and without lymph node (LN) metastasis and determined whether fibroblasts with different SDF-1alpha genotypes influenced cancer cell proliferation and migration. METHODS: The study enrolled 424 patients with primary T3 stage CRC, with and without lymph node metastasis, and a median follow-up of 48 months. The polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to identify polymorphisms. Fibroblasts were harvested from 14 patients with stage II CRC and fibroblast-mediated enhancement of cancer cell proliferation and migration was evaluated. RESULTS: Only the SDF1alpha-G801A polymorphism was associated with LN metastasis. The frequency of GA/AA genotypes was significantly higher in patients with LN metastasis (54.8%) than in patients without LN metastasis (40.7%). In the latter group, disease-free survival was shorter in patients with the GA/AA genotype (74%) than in patients with the GG genotype (87.6%). In patients with LN metastasis, disease-free survival was similar regardless of genotype. Expression of SDF-1alpha mRNA in GA/AA fibroblasts was three times that in GG fibroblasts. GA/AA (but not GG) fibroblasts enhanced colon cancer cell (HCT116) proliferation and migration. These effects were blocked by an SDF-1alpha neutralizing antibody. CONCLUSIONS: The SDF1alpha-G801A polymorphism may increase expression of SDF-1alpha mRNA and be a predictive marker of lymph node metastasis in colorectal cancer.
BACKGROUND: The SDF-1/CXCR4 axis plays an important role in cancer metastasis. SDF1alpha genetic polymorphisms, including SDF1alpha-G801A, have been associated with increased cancer risk and may be predictive of distant metastasis. The present study compared the frequency of 6 SDF1alpha single-nucleotide polymorphisms (SNPs) in patients with colorectal cancer (CRC) with and without lymph node (LN) metastasis and determined whether fibroblasts with different SDF-1alpha genotypes influenced cancer cell proliferation and migration. METHODS: The study enrolled 424 patients with primary T3 stage CRC, with and without lymph node metastasis, and a median follow-up of 48 months. The polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to identify polymorphisms. Fibroblasts were harvested from 14 patients with stage II CRC and fibroblast-mediated enhancement of cancer cell proliferation and migration was evaluated. RESULTS: Only the SDF1alpha-G801A polymorphism was associated with LN metastasis. The frequency of GA/AA genotypes was significantly higher in patients with LN metastasis (54.8%) than in patients without LN metastasis (40.7%). In the latter group, disease-free survival was shorter in patients with the GA/AA genotype (74%) than in patients with the GG genotype (87.6%). In patients with LN metastasis, disease-free survival was similar regardless of genotype. Expression of SDF-1alpha mRNA in GA/AA fibroblasts was three times that in GG fibroblasts. GA/AA (but not GG) fibroblasts enhanced colon cancer cell (HCT116) proliferation and migration. These effects were blocked by an SDF-1alpha neutralizing antibody. CONCLUSIONS: The SDF1alpha-G801A polymorphism may increase expression of SDF-1alpha mRNA and be a predictive marker of lymph node metastasis in colorectal cancer.
Authors: Karen Brajão de Oliveira; Roberta Losi Guembarovski; Alda Maria Fiorina Losi Guembarovski; Ana Cristina da Silva do Amaral Herrera; Walter Jorge Sobrinho; Carolina Batista Ariza; Maria Angelica Ehara Watanabe Journal: Clin Exp Med Date: 2012-06-15 Impact factor: 3.984
Authors: Tsz-Lun Yeung; Cecilia S Leung; Kay-Pong Yip; Chi Lam Au Yeung; Stephen T C Wong; Samuel C Mok Journal: Am J Physiol Cell Physiol Date: 2015-07-29 Impact factor: 4.249
Authors: Risala Hussain Allami; Claudine Graf; Ksenia Martchenko; Beatrice Voss; Marc Becker; Martin R Berger; Peter R Galle; Matthias Theobald; Thomas C Wehler; Carl C Schimanski Journal: Oncol Lett Date: 2016-01-25 Impact factor: 2.967
Authors: Jung Pyo Lee; Jong Bin Bae; Seung Hee Yang; Ran-Hui Cha; Eun Young Seong; Yang Jin Park; Jongwon Ha; Myoung Hee Park; Jin Ho Paik; Yon Su Kim Journal: PLoS One Date: 2011-02-03 Impact factor: 3.240