The supramolecular complex of Ad-HA/FA-M-β-CyD showed higher cytotoxic activity in HCT116 cells (FR-α (+), CD44 (+)), a human colon cancer cell line, than FA-M-β-CyD alone.
These results support the feasibility of an adenovirus-mediated RNA interference therapy targeting human colon cancer via the CD44 as a potential future therapeutic intervention.
In present investigation, we developed a novel hyaluronated cationic nanostructured lipid carrier (CNLCs) which contains CPT-11/irinotecan to target CD44 biomarker which commonly overexpresses on colon cancer.
Interestingly, we observed that, in contrast to breast cancer, loss of function p53 mutations were not associated with elevated CD44 expression in colon cancer.
We propose that the transition from CD44(-/low) to CD44(high) state helps to maintain a CD44(high) fraction and the tumorigenic diversity in colon cancer.
Expanded CRC colonospheres contained cells that expressed high levels of CD44 and CD166, which are markers of colon cancer stem cells, and had many features of cancer stem cells, including chemoresistance and radioresistance, the ability to initiate tumor formation, and activation of epithelial-mesenchymal transition (EMT).
In multivariate analysis CD44s, CD44v6, nuclear beta-catenin and CD68 expression was found to best discriminate left- versus right-sided colon cancers.
Endogenous miR-215 was elevated about 3-fold in CD133+HI/CD44+HI colon cancer stem cells that exhibit slow proliferating rate and chemoresistance compared to control bulk CD133+/CD44+ colon cancer cells.
The expression of endogenous miR-140 was significantly elevated in CD133(+hi)CD44(+hi) colon cancer stem-like cells that exhibit slow proliferating rate and chemoresistance.
In conclusion, based on this mouse xenograft model, siRNA targeting a discrete sequence of human CD44 may provide a potential therapeutic option for colon cancer.