Brian J. Nixon

Introduction. Colorectal cancer (CRC) involves the colon and/or rectum and usually starts off as growths called adenomatous polyps that have the ability to metastasize to distant organs⁴.  While there are many risk factors such as advanced age, history, and diet, the most critical factor affecting the 5-year survivorship rate is the stage⁵.  The 5-year survivorship rate for localized tumors is 89.8%, regional tumors 71%, and metastatic tumors, which have been implicated in 90% of CRC deaths, is 13.8%^3,5.  Studies demonstrate how the Wnt/β-catenin pathway plays a critical role in the development, progression, and metastasis of CRC by controlling the expression of many types of proliferative genes such as CD44 and its variant CD44v6^2,6.  Therefore, the primary purpose of this research was to investigate the function and expression patterns of CD44/CD44v6 in CRC, as well as the rationale for using it as a potential therapeutic target.  Methods.  HeLa cells were utilized to investigate whether CD44/variants were simply products of or products/modulators of the Wnt/β-catenin pathway.  Immunohistochemical analysis of resected human CRCs of various stages were analyzed for CD44v6 expression patterns, while microarrays were used to analyze CD44v6 expression in 402 primary CRCs taken from either the center or invasive fronts of those cancers⁹.  Results.  CD44 is a Wnt-targeted protein that also upregulates the Wnt/β-catenin pathway, while variant CD44v6 is strongly correlated with tumor progression in CRC⁷.  CD44v6 expression patterns as measured by immunoreactivity were:  minimal in normal tissue, maximal in adenoma, and moderate in primary carcinoma and liver metastasis⁹.  This loss of CD44v6 expression, and subsequent adhesive properties, was associated with more aggressive tumor type, perineural invasion, lymph node metastasis, and poorer prognosis⁹.  However, not all research supports this transition in CD44v6 expression, but rather suggests a constant expression pattern of CD44v6 regardless of stage of CRC⁹.  While in colorectal cancer stem cells (CRC-SCs), constant CD44v6 expression has consistently been strongly correlated with tumor progression and metastasis^1,8.  Conclusion.  Studies have demonstrated that CD44v6 plays a critical role in colorectal development, progression, and metastasis.  While there is some debate about whether CD44v6 expression varies with tumor progression, there is reliable data that demonstrates a constant expression pattern in CRC-SCs which are often involved in resistant and recurrent cancers.  Therefore, regardless of the exact expression pattern of CD44v6 and considering the significant decrease in 5-year survivorship of metastatic CRC, CD44v6 should garner intense clinical research efforts as a potential therapeutic target.

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