Tumour metastasis represents the most lethal aspect o f cancer. It involves initial attachment of cells to the extracellular matrix (ECM), degradation of the ECM and subsequent migration and detachment of cells from the ECM. This process depends on alterations in the expression of many key players including cell adhesion molecules (CAMs) and proteolytic enzymes such as the matrix metalloproteinases (MMPs). The MMPs are a large family of proteases collectively capable of degrading the entire ECM. CD44 is a multifunctional transmembrane adhesion molecule, which also plays a key role in cell signalling. The interactions between CAMs and MMPs are crucial therefore in controlling tumour cell invasion and metastasis and this study aimed to elucidate these interactions. We have established a panel of human colon cancer cell lines including a primary human colon adenocarcinoma cell line SW480 and its lymph node metastatic derivative, SW620. The SW480 cells have been stably transfected with the cDNA for MMP-7 (SW480M7) and MMP-9 (SW480M9). When the in vitro invasive activities of the cell lines were compared, the SW620 cells and the MMP transfected cells were more invasive than their parental SW480. The SW480M7 cells were more migratory in comparison to SW480 cells and interestingly, the SW620 were less migratory. MMP-9 expression increased when the SW480M9 cells were grown on HA and collagen. In addition, SW480M9 cells cultured in the presence of a CD44 activating antibody resulted in a time dependent increase in MMP-9 activity and increased invasion. The SW480M9 cells were shown to be the most adherent to plastic, HA and fibronectin and the SW480M7 were slightly less adherent. The increased HA adhesion in the SW480M9 correlated with increased 80kDa and 120kDa CD44 expression. cDNA microarray analysis was used to identify additional metastasis associated genes by examining and comparing differential gene expression profiles in these cell lines Analysis of gene expression data revealed that 233 genes were significantly up regulated and 208 genes were down regulated in the SW620 when compared to the SW480. Over expression of MMP-7 and MMP-9 in the SW480 cells also caused differential expression. Following literature searches on the gene lists, 5 genes of biological interest were chosen for further analysis and validation. Selected genes were the cysteine protease, cathepsin C, caveolin 1, the nuclear receptor, peroxisome proliferative activated protein gamma (PPARy), the ECM component tenascin C and asparagine synthetase. These clones were sequenced from the cDNA library to verify their identities and real time PCR analysis confirmed the fold changes in expression. Using a fluorescent assay, enhanced cathepsin C enzymatic activity in the SW620 cells was confirmed. A PCR-based method was also used to monitor the expression profiles of particular alternatively spliced tenascin C isoforms in the cell lines studied. An initial pilot study was conducted to examine expression of these genes in matched samples of normal and tumour colon tissue. RNA was extracted from tissues of varying Dukes’ classification and expression was examined by real time PCR. This study identified potential new biomarkers of colorectal metastasis, and examined the involvement of many key players in this process. This study demonstrated that interactions between CD44 and MMPs were important in controlling tumour cell invasion. It is hoped that this work will help elucidate the exact mechanisms of such interactions as well as highlighting their importance in the metastatic process. Further study on these biomarkers and interactions would validate their use as novel markers and therapeutic targets in metastatic colorectal disease.