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Constitutive expression of growth regulated oncogene (gro) in human colon carcinoma cells with different metastatic potential and its role in regulating their metastatic phenotype

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Abstract

The purpose of this study was to examine the expression and functional significance of the growth-regulated oncogene (gro) family in human colon carcinoma growth and metastasis. We examined constitutive expression of CXCL1 (gro-α), CXCL2 (gro-β), CXCL3 (gro-γ) and their receptor, CXCR2 in human colon carcinoma cells with different metastatic potentials. Non-metastatic and low metastatic cells expressed lower levels of CXCL1 and CXCR2 mRNA and protein as compared to high metastatic colon carcinoma cells. No difference in CXCL2 and CXCL3 mRNA expression levels was observed. Colon carcinoma cells expressing higher levels of CXCL1 exhibit increased proliferation and invasive potential. Furthermore, exogenous addition of recombinant human CXCL1 significantly enhanced the proliferation and invasiveness of colon carcinoma cells. Furthermore, treatment of KM12C cells with exogenous CXCL1 enhanced their invasiveness. Neutralizing antibody to CXCL1 in combination with antibody to CXCR2 inhibited highly metastatic KM12L4 (high CXCL1 expressor) cell proliferation. These data demonstrate that the constitutive expression of CXCL1 and its receptor CXCR2 is associated with metastatic potential and modulates colon cancer cell proliferation and an invasive phenotype.

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Abbreviations

ELISA:

enzyme-linked immunosorbent assay

FBS:

fetal bovine serum

gro :

growth regulated oncogene

IHC:

immunohistochemistry

RT-PCR:

reverse transcriptase-polymerase chain reaction

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Authors and Affiliations

  1. Department of Pathology and Microbiology, The University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE, 985845, 68198-7660, USA

    Aihua Li, Michelle L. Varney & Rakesh K. Singh

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  1. Aihua Li
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  2. Michelle L. Varney
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  3. Rakesh K. Singh
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Correspondence to Rakesh K. Singh.

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Li, A., Varney, M.L. & Singh, R.K. Constitutive expression of growth regulated oncogene (gro) in human colon carcinoma cells with different metastatic potential and its role in regulating their metastatic phenotype. Clin Exp Metastasis 21, 571–579 (2005). https://doi.org/10.1007/s10585-004-5458-3

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  • DOI: https://doi.org/10.1007/s10585-004-5458-3

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