Colorectal cancer is the second-leading cause of cancer-related deaths worldwide. Understanding tumor metastasis mechanisms and the interactions between cell types in the tumor microenvironment can help researchers identify treatment targets. Recently, a team of researchers examined the interaction between colorectal cancer cells and fibroblasts. IL-1α is a signaling protein that in other systems and cancers has both pro- and anti-metastasis effects. Here, the two highly metastatic colorectal cancer cell lines expressed IL-1α, while the less metastatic lines and fibroblasts did not. Increasing the abundance of IL-1α increased the expression of another signaling protein, CXCL12, in fibroblasts. This worked by either adding IL-1α directly or co-culturing fibroblasts with IL-1α-expressing cancer cells. Increasing the abundance of CXCL12, either directly or via co-culture, increased invasiveness of colorectal cancer cells and promoted angiogenesis. Blocking the IL-1α receptor with an antagonist (IL-1Ra) blocked the increased CXCL12 expression. While more research is needed, these results suggest that IL-1α and CXCL12 co-enhance the metastatic potential of cancer cells and that IL-1Ra can inhibit that metastatic increase via the IL-1α- and CXCL12-associated pathways.