Morphoproteomics Identifies CXCR4 in Undifferentiated Colorectal Cancer: A Case Study with Therapeutic Implications

Undifferentiated colorectal cancer (UCRC) has a well-documented CD44 cancer stem cell (CSC) component. CXCR4 (C-X-C motif receptor 4) also is a CSC marker and with its ligand, stromal-derived factor (SDF)-1 alpha has been shown to act in concert with CD44 to promote cancer cell invasion. To date, CXCR4 has not been reported in the MEDLINE (PubMed) literature with respect to UCRC. Morphoproteomic analysis, utilizing bright field microscopy, can visualize the intensity and cell location of protein analytes with a patient's tumor including CXCR4 expression and was applicable to this case study. Using morphoproteomic analysis we identified chromogenic expression of both CD44 on the plasmalemmal aspect of the majority of the undifferentiated colorectal cancer foci and CXCR4 expression on the plasmalemmal or cytoplasmic aspect in up to 50% of the tumor cells in some regions and also on the intratumoral endothelial cells in the patient's UCRC. Moreover, both CSC markers were retained in the foci showing incomplete mucinous differentiation. In the context of data mining of the scientific literature, these findings suggest a collaboration between CXCR4 and CD44 in promoting tumor invasion and angiodependent metastasis in UCRC. Therapies designed to inhibit both the CD44 and the CXCR4 pathways are available and could reduce the metastatic potential of UCRC.