GROα promotes invasion of colorectal cancer cells

Abstract

Growth-regulated oncogene alpha (GRO alpha) is a chemokine that plays a role not only in inflammation, but also in tumorigenesis. Accumulating data suggest that GRO alpha is involved in tumor development and invasion in various malignancies, such as melanoma and bladder cancer. However, the pathophysiological role of GRO alpha in human colorectal cancers (CRCs) is still unknown. We examined the expression of GRO alpha and its pathophysiological significance in human CRCs and investigated whether GRO alpha promotes the invasive potential of colon cancer cells. Specimens of 62 primary CRCs were examined immunohistochemically for GRO alpha, and the relationship between GRO alpha expression and clinicopathological features was investigated. The mRNA expression of GRO alpha and its receptor CXCR2 was examined in ten colon cancer cell lines using RT-PCR. The effect of GRO alpha protein on invasive potential was investigated in DLD-1 and LoVo cells using a Matrigel invasion chamber assay. Forty-nine (79%) of the 62 CRCs showed positive immunoreactivity for GRO alpha. GRO alpha expression was significantly associated with tumor size, tumor stage, depth of invasion, LN metastasis and patient survival (P=0.021, P<0.0001, P=0.0033, P<0.0001, P=0.039, respectively). Expression of CXCR2 mRNA was detectable in all ten colon cancer cell lines examined, whereas expression of GRO alpha mRNA was detectable in six. Treatment with GRO alpha protein significantly increased the number of invasive cells. In conclusion, GRO alpha may play a pivotal role in the invasion of human CRCs.